SecProbe.io

August 3, 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. 3 to Registra tion Statement on Form S-1
Filed July 20, 2011
  File No. 333-173420

Dear Mr. Pandolifino:
 We have reviewed your responses to the co mments in our letter dated July 14, 2011 and
have the following additional comments.  All page numbers below correspond to the marked
version of your filing.

Prospectus Summary, page 1

 Our Company, page 1

 Overview, page 1

1. Please revise to reconcile your disclosure  in the second sentence on page 1 “that you
control 90 issued patents” with your disclosu re in the same sent ence that, of those 90
issued patents, “[you] own 8 issued patents” and “have control of an additional 90 issued
patents” and with your disclosure on page 5 that your “proprietary technology is covered
by 12 patent families consisting of 98 issued patents.”

2. Please revise to clarify the expiration dates of your two exclusive licenses if none of the
patent applications under each  license is successful.

3. We note your disclosure in the last sentence on page 1 and in the first paragraph on page
36 that your “very low nicotin e (VLN) cigarettes made fr om [your] VLN tobacco have
already demonstrated efficacy in previous Phas e II trials, specifically  the Phase II trial at
the University of Minnesota which had a very  similar protocol to our upcoming Phase II
clinical trial.”  Please revise this disclosure to clarify that further research is needed to
determine the efficacy of X-22.

Joseph Pandolifino 22nd Century Group, Inc. August 3, 2011 Page 2

 4. We note your response to our prior comment one .  Please revise the first sentence in the
fourth paragraph on page two and the first se ntence in the third paragraph on page 36 to
clarify that further research is need ed to determine the efficacy of X-22.

5. Please refer to the first sentence in the first pa ragraph on page three.  Please explain to us
the basis for your belief stated here a nd elsewhere that BRAND A and BRAND B will
qualify as Modified Risk Cigare ttes, given that the FDA has not  yet issued its regulations
and guidance in this regard.

Risk Factors, page 9

 The FDA requirement regarding graphic health warnings, page 19

6. We note your response to our prio r comment eight.  Please revise this risk factor and your
Government Regulation disclosure to also address which of your current products or
products in development will be subject to these new packaging and advertising
regulations.

Business, page 35

“Tar” Nicotine and Smoking Behavior, page 37

7. We note your response to our prior comment one.   We note your disclosure on page 38
that “[s]tudies have shown that smokers do not compensate when smoking cigarettes
made with our VLN tobacco, and that smoking VL N cigarettes, such as Brand A, actually
assist smokers to smoke fewer cigarettes pe r day and reduce their exposure to certain
tobacco smoke toxins, including nicotine.”  Please revise to clarify that further studies are
needed to verify the claims made in this st atement.  In addition, we note that your intent
is to sell Brand A as modified risk cigare tte and not as a smoking cessation aid.  Please
revise or advise.

8. We note your response to our prior comment one.  Please revise the last sentence in this
section on page 38 to remove the words “such as Brand B” and revise to clarify that
Brand B was not used in these studies and that  further studies are needed to verify your
statements regarding Brand B.

Market, page 38
 Cigarettes and Smoking Cessation Aids, page 38

9. We note your response to our prior comment one.  Please revise the last sentence in the
first paragraph of this section to clarify that  further studies will need to be done in order
to determine whether your products can  meet the identified needs.

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

 10. We note your response to our prior co mment nine.  Please refer to the  third  paragraph in
this section on page 38.  With a view to revised disclo sure, please tell us how the
information cited earlier in  the paragraph provides a basis for your conclusion  that X-22
will be attractive to smokers “especially with  those who have previously attempted to
quit and failed.”

11. Please remove the word “limited” in th e fourth paragraph in this section.
 Products, page 39

 X-22 Smoking Cessation Aid, page 39

12. Please revise the last four bullet points on page  40 given that that further study is needed
to demonstrate efficacy.

Brand B Cigarettes, page 42

13. We note your response to our prior comment one .  Please refer to the first paragraph on
page 42.  Please revise to clarify that huma n studies still need to be conducted to
determine the level of carbon monoxide exposur e and the level of nicotine exposure from
smoking BRAND B, or please advise.

Research and Development, page 55

14. Please revise to remove the words “highly qualified.”

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. August 3, 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