SecProbe.io

July 14, 2011
 Via E-mail

Joseph Pandolifino Chief Executive Officer 22nd Century Group, Inc. 8201 Main Street, Suite 6 Williamsville, NY 14221
Re: 22nd Century Group, Inc.
  Amendment No. 2 to Registra tion Statement on Form S-1
Filed June 29, 2011
  File No. 333-173420

Dear Mr. Pandolifino:
 We have reviewed your responses to the co mments in our letter dated June 22, 2011 and
have the following additional comments.  All page numbers below correspond to the marked
version of your filing.

General

1. We note your response to our prior comment one.  Please revise throughout to provide
balancing disclosure to clarify that furthe r research of your products is needed to
determine efficacy as we note that the abstr acts of the reports you pr ovided in response to
our prior comment one suggest th at results are preliminary and further research is needed.
In addition, we note that your conclusions re garding the effectiveness of Brand B are
based upon studies that utilized products other than Brand B.  We also note that you have
not yet completed the FDA approval process.  For example, we note the fourth sentence
in the second paragraph on page two, statem ents on pages two and elsewhere that your
products do not expose users to any new side effects, the fi rst sentence in the third
paragraph on page two, the second sentence in the first paragraph on pa ge three, the first
sentence in the second paragraph on page 36, th e last two sentences in the first paragraph
on page 38, the last sentence of the second paragraph on page 38, the bullet points on
page 39, the third sentence in the first paragraph on page 41, the third paragraph on page
41, statements in the first paragraph on pa ge 42, the graph on page 42 and the paragraph
preceding the graph, the third sentence of th e third paragraph on page 42, the discussion
“Clinical Trials with Cigarettes Cont aining our VLN Tobacco” beginning on page 43,
claims regarding Rubisco in the third and fourth paragraph on page 55, and claims
regarding Verfola in the fourth and fifth paragraphs on page 55.

2. In this regard, we note your di sclosure in the second sentence  of the “Brand A Cigarettes”
section on page 41 that “[c]linical studies have demonstrated” and your disclosure on

Joseph Pandolifino 22nd Century Group, Inc. July 14, 2011 Page 2

 pages 43 to 46 regarding the result s of various clinical trials.  Please advise as to whether
the reports containing the results of these clinic al trials are publicly available.  If the
reports are not publicly available, please provi de a consent of the au thor under Rule 436
of the Securities Act of 1933.
 Prospectus Summary, page 1

 Our Company, page 1

 Overview, page 1

3. Please revise to clarify your disclosure on page two and else where that you believe that
your VLN tobacco “does not present any new side  effects.”  We note that it appears that
the tobacco would cause many of the same side effects as smoking a non-VLN tobacco
cigarette.  In this regard pl ease also note comment one above.

4. We note your response to our prior comment 25 and your disclosure on page 1 that you
plan to raise approximately $15,000,000 in Fall 2011 to fund Phase III trials, modified
risk exposure studies and for your general worki ng capital requirements.  Please revise to
disclose here how you intend to raise such funds.

5. We note your response to our prior comments 20 and 22.  Please revise the last sentence
in the first paragraph of the “Overview” secti on on page one to indicate that you have not
identified any specific countries or devel oped any timelines or cost estimates for
international expansion.

Smoking Cessation Aids, page 3

6. Please remove the words “such as X-22” from the first sentence in this section, as The
Tobacco Control Act does not sp ecifically address your product.

Technology Platform and Inte llectual Property, page 4

7. We note your response to our prior comment 16 and reissue in part.  Please revise your
disclosure on page 5 to clarify what you m ean by your “two worldw ide exclusive licenses
expire upon the last-to-expire patent on a country-by-country basis, which is from 2022
through 2026.”

Risk Factors, page 9

8. Please add a risk factor di scussing how FDA requirements requiring graphic health
warnings may impact sales of your products, as applicable.  Pleas e also revise the
Government Regulation section be ginning on page 51 as appropriate.

Joseph Pandolifino 22nd Century Group, Inc. July 14, 2011 Page 3

 Business, page 35

 Market, page 38

 Cigarettes and Smoking Cessation Aids, page 38

9. Please provide a basis for statements in the fi rst three sentences in the third paragraph and
the first sentence in the fourth paragraph in  this section and the second sentence in the
last paragraph on page 40.  Additionally, pleas e revise to disclose the date of these
statistics.

10. Please revise the second to the last paragr aph on page 38 to clarify that there is no
guarantee that, even if approved by the F DA, X-22 will have comparable sales to
Chantix, or that  the FDA will not re quire X-22 to have a boxed warning.
 Government Regulation, page 51

 Clinical Phase, page 51

11. We note your disclosure on page 52 that you have designated your upcoming phase II
clinical trial as a “Phase II-B  trial.”  Please revise to clarify whether this is your
designation or if the FDA has also designated th e trial as a Phase II-B trial, or please
advise.

We urge all persons who are responsible for th e accuracy and adequacy of the disclosure
in the filing to be certain that the filing incl udes 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 disc losure, 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 date
of the pending registration statement please pr ovide a written statement from the company
acknowledging that:

 should the Commission or the staff, acting purs uant to delegated authority, declare the
filing effective, it does not foreclose the Co mmission 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

Joseph Pandolifino 22nd Century Group, Inc. July 14, 2011 Page 4

  the company may not assert staff comments a nd 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 re quests for acceleration.  We will consider a
written request for acceleration of  the effective date of the regi stration statement as confirmation
of the fact that those reques ting acceleration are aware of thei r respective responsibilities under
the Securities Act of 1933 and the Securities Excha nge Act of 1934 as they relate to the proposed
public offering of the securities specified in th e above registration stat ement.  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,
    /s/ John Dana Brown    John Dana Brown
Attorney-Advisor
cc: Via E-mail

             Patrick G. Quick              Foley & Lardner LLP