SecProbe.io

June 22, 2011
Joseph Pandolifino
Chief Executive Officer
22nd Century Group, Inc.
8201 Main Street, Suite 6 Williamsville, NY 14221

Re: 22nd  Century  Group, Inc.
  Amendment No. 1 to Registration Statement on Form S -1
Filed  June 7 , 2011
  File No.  333-173420
 Dear Mr. Pandolifino:
 We have reviewed your responses to the comments in our letter dated May 6, 2011 and
have the following additional comments.  All page numbers below correspond to the marked
version of your filing.

General

1. We note statements throughout regarding the effectiveness of the products you are developing.  Please tell us whether such statements are appropriate given that you have not yet completed the FDA approval process. Additionally please tell us your basis for statements throughout regarding the limited effectiveness or side -effects of competing
products.

Registration Statement Cover Page

2. Please revise to indicate the Primary Standard Industrial Classification Code as 2111 or
advise.

Prospectus Summary, page 1

Our Company, page 1

Overview, page 1

3. We note your response to our prior comment 33.  Please revise to state here that you are
currently in default pursuant to the terms of your exclusive worldwide license agreement with North Carolina State University.  P lease indicate that if NCSU chooses to invoke
any right it may have to terminate the License Agreement and you ar e unable to cure the
default, your business would be materially and adversely affected.  Please additionally

Joseph Pandolifino
22nd Century Group, Inc. June 22, 2011
Page 2

state that if NCSU does not agree to continue to defer payment of the balance, you may not have sufficient funds to pay for the Phase II -B clinical  trial for X -22 in full.

4. We note your response to our prior comment four and reissue in part.  Please revise to include your net loss from your most recent interim stub and audited period.

5. We note your response to our prior comment eight and reissue in part.  Please provide support to us for your statement on page 2 that X -22 is the only smoking cessation
product that functions exactly like a regular cigarette.

6. Please provide support to us  that every FDA -approved smoking cessation aid since the
establishment of the Fast Track program in 1997 has received the Fast Track designation.  Alternatively, please remove this statement.

7. Please revise the last sentence in the second paragraph on page  4 to clarify that you do
not have an agreement with RTI or other researchers to purchase additional SPECTRUM cigarettes.

8. Please provide support to us for your statement on page 4 that your tobacco contains the lowest nicotine content of any tobacco ever commercialized.  Alternatively, state this as a belief.

9. We note your statement on page 4 that “ analyses by an independent accredited laboratory
found that the levels of certain compounds in the tobacco leaf of the genetically engineered variety were not substantially different than that of conventional tobacco,
except for reduction in nicotine and related compounds.”  Please state as to whether the report containing these analyses is publicly available.
In addition, if this report was not
available for f ree or for a nominal fee, please provide a consent of the author to be named in
the registration statement under Rule 436 of the Securities Act of 1933.

10. We note your disclosure in the fourth paragraph on page 4 that you expect your patent applications to  cover your products until 2024 to 2026.  Please revise to clarify that there
is no guarantee that the patent applications will cover your products.

11. We note your response to our prior comment 11.  Please revise the statement on page F -
16 regarding  “each such PPO Security consisting of one (1) Unit and a five -year warrant
to purchase one -half of one (1/2) Unit at an exercise price of $1.50 per whole Unit”
accordingly.

Risk Factors, page 8

12. We note your response to our prior comment 12 and reissue.  P lease remove the words
“although there may be other risks th at could arise or may prove to be more significant
than expected, that may affect our operation or financial results ” from the third  sentence

Joseph Pandolifino
22nd Century Group, Inc. June 22, 2011
Page 3

of the introductory paragraph of this section, and ple ase remove the fourth  sentence from
the introductory paragraph of this section .  If risks are not deemed material then they
should not be mentioned.

13. We note your response to our prior comment 13.  Please tell us what consideration you have given to providing a risk factor addressing that this product when marketed previously resulted in “relatively low” sales volume.

We will incur increased costs and demands upon management as a result of complying, page 22

14. Please revise to disclose the costs associated with complying with the laws and
regulation s affecting public companies.

Business, page 33

Overview, page 33

15. We note your response to our prior comment 20.  Please further provide us a basis for
your belief that you “will enable us to capture a significant share of the global market for
approved smoking cessation aids and the emerging market for modified risk tobacco products .”  Additionally , please revise the second paragraph on page two to indicate that
there is no guarantee that you will  be ab le to “take sales and market share from existing
smoking cessation products” and “expand the smoking cessation market.”

16. We note your response to our prior comment 21 and reissue.  Please revise to clarify the number of patents that you own and the num ber of patents that you license.  In addition,
please revise to clarify what you mean on page 33 that your “two worldwide exclusive licenses expire upon the last -to-expire patent on a country -by-country basis.”

Market, page 36

17. We note your response to our prior comment 22 and reissue in part.  Please tell us why the 2008 Datamonitor forecast in the second paragraph on page 36 is still reliable.

Products, page 37

X-22 Smoking Cessation Aid, page 37

18. Please revise the second to the last sentence in the second paragraph on page 38 to clarify that you have not taken any steps to obtain approval for X -22 outside of the United
States.

Joseph Pandolifino
22nd Century Group, Inc. June 22, 2011
Page 4

Brand B Cigarettes, page 39

19. Please revise the statement in the seco nd paragraph on page 40 that “[w]e believe that
evaluation of BRAND B in short -term human exposure studies will confirm…” given
that these studies have not been completed.

Sales and Marketing, page 45

X-22 Smoking Cessation Aid, page 45

20. We note your disclosure on page 45 that you intend to enter into arrangements in both the U.S. and international markets with pharmaceutical companies to market X -22 before
completion of the Phase III clinical trials.  P lease revise to disclose whether you have
identified any  countries where you intend to attempt to have X -22 approved for
commercial sale.  Additionally , please include timelines and costs  for this international
expansion.

21. Please revise to clarify what you mean by “measured approach” in th e first paragraph of
this section.  In addition, please revise the references  to “wherewithal” on page 45 to
indicate more clearly what resources licensing parties will be required to have.

Brand A and Brand B, page 45

22. We note that you expect to begin marketing your Brand A and Brand B cigarettes internationally in approximately 2 years.  P lease revise to disclose where you intend to
sell your products  and advise as to whether you will need to go through an approval
process to sell your Brand A and Brand B cigarettes  in such countries .  To the extent that
you will need to obtain approval, please disclose.

Government Research Cigarettes, page 46

23. We note your response to our prior comment 27 and reissue in part.  Please revise here and in the second paragraph on page four  to clarify that there is no guarantee that you
will receive  additional orders from RTI or from other researchers or advise.

Potential Smoking Cessation Aids, page 47

24. Please provide support to us for your disclosure in the third par agraph on page 47
regarding the vaccine treatment tests.  In addition, please tell us why Dr. Fiore’s estimate regarding the approval of a nicotine vaccine in 2009 is reliable.

Joseph Pandolifino
22nd Century Group, Inc. June 22, 2011
Page 5

X-22 Clinical Trials, page 51

25. We note your response to our prior comment 30 and reissue in part.  Please revise to disclose whether you have any plans for raising the additional funding you will need for the Phase III clinical trials.

Biomass Products, page 52

26. Please revise to disclo se a brief description of your biomass business plan, including a
timeline and costs.

Exhibit Index, page E -1

27. Please revise to include all of the exhibits that are included in your registration statement here.

Exhibit 5.1

28. Please have counsel revise the last paragraph of the opinion letter by removing the first sentence as it is inappropriate to limit reliance.

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 1933 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 disc losures they have made.

Notwithstanding our comments, in the event you request acceleration of the effective date
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 action 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 accuracy of the 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.

Joseph Pandolifino
22nd Century Group, Inc. June 22, 2011
Page 6

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 offer ing of the securities specified in the above registration statement.  Please allow
adequate time for us to review any amendment prior to the requested effective date of the registration statement.
 Please contact Sonia Bednarowski at (202) 551 -3666 or  me at (202) 551 -3859 with any
questions.
Sincerely,

  John Dana Brown
Attorney -Advisor

cc: Via facsimile: (414) 297 -4900
             Patrick G. Quick
             Foley & Lardner LLP