SecProbe.io

February 28 , 2013

Via E -mail
Joseph Pandolfino
Chief Executive Officer
22nd Century Group, Inc.
9530 Main Street
Clarence, NY  14031

Re: 22nd C entury Group, Inc.
  Registration Statement on Form S-1
Filed  February 4, 2013
  File No.  333-186449

Dear Mr. Pandolfino :

We have limited our review of your registration statement to those issues we have
addressed in our comments.  In  some of our comments, we may ask you to provide us with
information so we may better understand your disclosure.

Please respond to this letter by amending your registration statement and providing the
requested information .  Where you do not believe our comments apply to your facts and
circumstances or do not believe an amendment is appropriate, please tell us why in your
response.

After reviewing any amendment to your registration statement and the information you
provide in response to these  comments, we may have  additional comments.

General

1. Prior to printing and distribution of the preliminary prospectus, please provide us with
mock -ups of any pages that include any pictures or graphics to be presented.
Accompanying captions, if any, should also be provided.  We may have comments after
reviewing the material.

Registration Statement Cover Page

2. We note that you are registering the resale of 27,500,000 shares of your common stock
on a delayed or continuous basis pursuant to Rule 415 of the Securities Act of 1933.
Given the size of the offering relative to the number of shares of your common stock
outstanding held by non -affiliates, the nature of the offering and the selling stockholders,
the transaction appears to be a primary offering .  Because you are not eligible to conduct

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 2

 a primary offering on Form S -3, you are not eligible to conduct a primary at -the-market
offering under Rule 415(a)(4) of the Securities Act of 1933 .  If you disagree with our
analysis, please advise regarding  your basis for determining that the transaction is
appropriately characterized as a transaction that is eligible to be made under Rule
415(a)(1)(i) of the Securities Act of 1933 .  In your analysis, please address the following
among any other relevant factors :

 The number of shares of your common stock outstanding held by non -affiliates prior
to the private placement of the Series A -1 Preferred Stock and Series A, B and C
Warrants on January 11, 2013;
 The dollar value of the shares of common stock registered i n relation to the proceeds
that you received from the selling stockholders for the securities, excluding amounts
of proceeds that were returned (or will be returned) to the selling stockholders and/or
their affiliates in fees or other payments;
 The relationship of each selling stockholder with the company, including an analysis
of whether each selling stockholder is an affiliate of the company; and
 Whether or not any of the selling stockholders are in the business of buying and
selling securities.

3. We note the reference to Rule 416  of the Securities Act of 1933  in footnote 1 to the fee
table.  Please confirm that you understand that issuing additional shares because of
changes in the stock price is not covered by the transactions involving Rule 416.

Prospectus Summary, page 1

Overview, page 1

4. We note your disclosure in the first and second paragraphs only briefly discusses your
two primary lines of business related to (i) smoking cessation products and (ii) premium
cigarettes and modified risk tobacco products.  Please revise to provide a more detailed
summary of your business and current operations.

5. Additionally, we find missing from the summary the picture of the company revealed in
the Risk Factor  and Business sections on page 7 and 27  of a company facing financial
difficulties  and which has recently limited certain operations .  For example, we note that
you have suspended further clinical trials for FDA approval of your X -22 smoking
cessation product and that you will need significant additi onal capital to complete the
FDA authorization process for your modified risk cigarettes.  We also note that you are
limited in your abilities to raise additional capital due to your outstanding Series A -1
Preferred Stock.  Please revise the summary so tha t the narrative discussion reflects what
appears to be a challenging time for the company .

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 3

 6. Please revise to disclose in the summary the failure of X -22 in the most recent test and
the effect that failure has had upon your situation.

7. We note your disclos ure in the second paragraph that in March 2011 you introduced two
of your own products, RED SUN and MAGIC cigarettes, into the U.S. market.  Please
revise this paragraph to disclose the revenue and net income or loss that you have
realized from these produ cts during the most recent audited and interim period s.  To the
extent these products have only been introduced into the U.S. market in a limited
capacity, please revise to disclose such fact.

Current Financial Condition, page 1

8. Please revise the first paragraph to disclose that your auditors  have  issued a going
concern opinion on your audited financial statements.

9. Please bold the last sentence of the first paragraph and update in the  next amendment.

10. We note your disclosure in t he second paragraph that your expected capital requirements
over the next 12 months without any extraordinary expenses are approximately $1
million.  We also note that your September 30, 2012 balance sheet list s significant
accounts payable, accrued expens es, a demand bank loan, and notes  payable and
convertible notes payable as compared to your limited cash position.  In this regard, we
note that $1.3 million of convertible notes payable mature in April of 2013.  Please
confirm that this section accurately  discloses your near -term capital requirements and
detail the requirements and expected uses of such funds.

11. We note your disclosure in the fourth risk factor on page 7 that the certificate of
designation of your Series A -1 Preferred Stock contains restric tive covenants that limit
your ability to incur or assume additional debt or provide guarantees in respect of
obligations of other persons.  Please revise the second paragraph to disclose this
limitation on your ability to raise capital and include a cross  reference to the fourth risk
factor on page 7.

Risk Factors, page 7

12. We note your disclosure in the first paragraph of this section of “[t]he following
discussion addresses those risks that management believes are the most significant,
although there may  be other risks that could arise or may prove to be more significant
than expected, that may affect our operations or financial results.”  All material risks
should be discussed in this section.  This section should not reference unknown or
immaterial risks.  Please revise  this paragraph to clarify that you have discu ssed all
known material risks.

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 4

 We have had a history of losses, and we may be unable to achieve or sustain profitability, page 7

13. We note your disclosure that you expect to continue to incur net losses and negative
operating cash flows in the foreseeable future.  Please revise to quantify the amount of
net losses that you expect to incur in to the foreseeable future or alternatively qu antify
your monthly “burn rate.”

14. We note your disclosure that you will need to spend significant capital to fulfill planned
operating goals and conduct clinical studies, achieve regulatory approvals and, subject to
such approvals, successfully produce products for commercialization.  Plea se revise to
quantify these long-term capital requirements .  Please also revise the Overview and
Current Financial Condition sections  on page 1 to discuss and quantify such long-term
capital requirements.

Business, page 27

15. We note your disclosure through out this section with respect to your future business
plans  and products , such as completing additional clinical trials related to X -22, obtaining
FDA approval of X -22 as a smoking cessation product and obtaining FDA approval of
Brand A and Brand B cigaret tes as modified risk tobacco products.  To the extent that
you discuss future business plans  or the development of future products  in this section,
the discussion should be balanced with a brief discussion on the time frame  for
implementing future plans  and finalizing the development of  future products , the steps
involved, the associated costs, and any obstacles involved before you can commence the
planned operations.  This includes the need for any additional financing.  If additional
financing may not be available, please clarify that.   In this regard, we note your
disclosure in the fourth risk factor on page 8 disclosing certain cost estimates and the first
risk factor on page 12 disclosing certain FDA approval time frame estimates related to
your futu re plans  and products .  Please also revise the Prospectus Summary on page 1 so
that investors can clearly understand your future business plans and the development
status of your future products to include timing and cost s.

Overview, page 27

16. We note your  disclosure in the fifth paragraph that you believe that X -22, upon the
completion of additional clinical trials that demonstrate efficiency, can capture significant
share of the smoking cessation product market.  Please revise to add balancing language
that there is no guarantee that you will obtain the funds necessary to complete additional
clinical trials, that you will obtain necessary FDA approvals and that will capture
significant share of the smoking cessation product market.

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 5

 Smoking Cessation Ai ds, page 28

17. We note your disclosure in the last sentence that you believe X -22, upon the completion
of additional clinical trials that demonstrate efficiency, will qualify for “Fast Track”
designation by the FDA.  We note that X -22 has in the past already  been denied “Fast
Track” designation by the FDA.  Please revise to add balancing language that there is no
guarantee that the FDA will grant “Fast Track” designation to X -22.  Please also include
a cross reference to the Fast Track Development section on page 41.

Modified Risk Cigarettes, page 28

18. We note your disclosure that you believe Brand A and Brand B will achieve significant
market share in the global cigarette market among a specified subgroup of smokers.
Please revise to add balancing language t hat there is no guarantee that you will obtain
necessary FDA approvals and that you will achieve a significant market share of this
specified subgroup of smokers.

Tar, Nicotine, and Smoking Behavior, page 29

19. We note your disclosure in the last sentence of the second paragraph that studies have
demonstrated that compensatory smoking of low -tar research cigarettes, similar to Brand
B, is greatly curtailed resulting in smokers inhaling less “tar” and carbon monoxide.
Please revise to add balancing language  that Brand B was not used in such studies and
that additional studies may be necessary to establish whether Brand B cigarettes achieve
similar result s.

Products, page 31

Brand A Cigarettes, page 32

20. We note your disclosure in the last paragraph that you  believe Brand A will receive a
modified risk cigarette classification  from the FDA.  Please revise to add balancing
language that there is no guarantee that the FDA will grant such classification .  Please
revise the Brand B Cigarettes section on page 32 i n a similar manner.

Brand B Cigarettes, page 32

21. We note your disclosure that Brand B cigarettes’ smoke contains the lowest amount of
“tar” per milligram of nicotine compared to other commercial tobac co cigarettes.  Please
provide  us with support for this  statement or revise.

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 6

 RED SUN and MAGIC  Cigarettes, page 33

22. We note your disclosures in footnotes 2 to your audited and interim financial statements
that you are still exploring distribution channels for your RED SUN and MAGIC
cigarettes and that you are not currently taking orders for these products in the U.S.
market.  Please revise this section and the Overview section on page 1 as applicable.
Please include enough information so that investors can understand the status of these
products.

Sales and Marketing, page 36

23. Please revise to disclose when you intend to begin marketing each product and the
expected costs.

Management’s Discussion and Analysis of Financial Condition, page 44

Liquidity and Capital Resources, page 48

Cash demands on opera tions, page 48

24. We note your disclosure in the first paragraph that your cash position is insufficient to
maintain your operations for the next 12 months.  Please revise to quantify your expected
near term and long term financing requirements which are nec essary to maintain your
current operations and to implement your future business plans .

Description of Securities, page 64

General, page 64

25. We note that you qualify the summary of your capital stock by the provisions of
applicable law.  Such a qualifica tion is inappropriate unless you file the applicable
provisions as exhibit s to the registration statement.  Please revise accordingly.

Exhibit 5.1

26. We note that the r egistration statement registers  shares of the company’s common stock
issuable (i) upon conversion of the Series A Preferred Stock, (i i) as dividends on the
Series A Preferred Stock and (iii) upon exercise of the Series A, B and C Warrants.  We
also note that counsel has only opined upon  the securities mentioned in clauses (i) and
(iii) above.  Please have counsel revise the opinion to opine that the  shares of common
stock issuable as dividends on the Series A Preferred Stock  will be validly issued, fully
paid and non -assessable .

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 7

 We urge all persons who are responsible for the accuracy and adequacy of the disclosure
in the filing to be certain that the filing includes the information the Securities Act of 193 3 and
all applicable Securities  Act rules require.  Since the company and its management are in
possession of all facts relating to a company’s disclosure, they are responsible for the accuracy
and adequacy of the disclosures they have made.

Notwithstanding our comments, in the event you request acceleration of the effective da te
of the pending registration statement please provide a written statement from the company
acknowledging that:

 should the Commission or the staff, acting pursuant to delegated authority, declare the
filing effective, it does not foreclose the Commission  from taking any act ion with respect
to the filing;

 the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective, does not relieve the company from its full responsibility for
the adequacy and accura cy of th e disclosure in the filing; and

 the company may not assert staff comments and the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal
securities laws of the United States.

Please  refer to Rules 460 and 461 regarding requests for  acceleration .  We will consider a
written request for acceleration of the effective date of the registration statement as confirmation
of the fact that those requesting acceleration are aware of their respective responsibilities under
the Securities Act of 1933 and the Securities Exchange Act of 1934 as they relate to the proposed
public offering of the securities specified in the above registration statement.  Please allow
adequate time  for us to revie w any amendment prior t