United States securities and exchange commission logo

                           May 11, 2021

       Robert B. Bazemore
       President and Chief Executive Officer
       Epizyme, Inc.
       400 Technology Square, 4th Floor
       Cambridge, Massachusetts 02139

                                                        Re: Epizyme, Inc.
Statement on Form S-3
                                                            Filed May 6, 2021
                                                            File No. 333-255806

       Dear Mr. Bazemore:

              This is to advise you that we have not reviewed and will not
review your registration

               Please refer to Rules 460 and 461 regarding requests for
acceleration. We remind you
       that the company and its management are responsible for the accuracy and
adequacy of their
       disclosures, notwithstanding any review, comments, action or absence of
action by the staff.

                                                        Please contact Irene
Paik at 202-551-6553 with any questions.


                           Division of Corporation Finance

                           Office of Life Sciences
       cc:                                              Molly W. Fox