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 April 16, 2025

David D. Halbert
Chairman, Founder & Chief Executive Officer
Caris Life Sciences, Inc.
750 W. John Carpenter Freeway
Suite 800
Irving, TX 75039

 Re: Caris Life Sciences, Inc.
 Amendment No. 4 to Draft Registration Statement on Form S-1
 Submitted April 4, 2025
 CIK No. 0002019410
Dear David D. Halbert:

 We have reviewed your amended draft registration statement and have the
following
comments.

 Please respond to this letter by providing the requested information and
either
submitting an amended draft registration statement or publicly filing your
registration
statement on EDGAR. If you do not believe a comment applies to your facts and
circumstances or do not believe an amendment is appropriate, please tell us why
in your
response.

 After reviewing the information you provide in response to this letter
and your
amended draft registration statement or filed registration statement, we may
have additional
comments.

Amendment No. 4 to Draft Registration Statement on Form S-1
Risk Factors
We have been, are currently, and in the future may be the subject of government
investigations, claims, audits, whistleblower and payer..., page 57

1. We note your disclosure that "in March 2025, the Company received a CID
from the
 DOJ in connection with an investigation under the False Claims Act
regarding the
 Company's compliance with Medicare's date of service rule (also referred
to as the 14-
 day rule)." Please revise to provide additional background regarding the
CID, the
 scope of the investigation and your compliance with Medicare's date of
service rule.
 April 16, 2025
Page 2

Management's Discussion and Analysis of Financial Condition and Results of
Operations
Results of Operations
Molecular Profiling Services Revenue, page 117

2. We note the many references in your filing to over 45 NCI-designated
comprehensive
 cancer centers being members of the Caris POA and these centers appear
to be "key
 opinion leaders." We note here the increased market acceptance by
ordering
 physicians. Please tell us the number of NCI-designated comprehensive
cancer centers
 that have ordering physicians, for each period presented, and the
consideration you
 have given to discussing this and any related information pursuant to
Item 303 of
 Regulation S-K.
Business
Our Strategies, page 146

3. We note your disclosure on page 147 that "[you] are currently using an
AI/ML
 approach and data and slides images from more than 10,000 breast cancer
patients to
 develop ESPai, a new algorithm to predict the risk of recurrence for
early stage breast
 cancer patients." Please revise to clarify the current stage of
development of ESPai,
 and explain how you source the data and slide images from more than
10,000 breast
 cancer patients.
Caris Strategic Data, page 170

4. We note your disclosure on page 172 regarding a study that you recently
published,
 which "demonstrated the power of [y]our real-world clinical and genomic
dataset,
 augmented through agreements with external providers of clinical
outcomes data, to
 drive clinical insight". Please revise to provide additional detail
regarding the study
 including: the date(s) and location(s) of the study; how participants
were
 selected; how results were measured; key assumptions; and whether
statistical
 significance was demonstrated, including supporting p-values, as
appropriate.
 Please contact Tayyaba Shafique at 202-551-2110 or Michael Fay at
202-551-3812 if
you have questions regarding comments on the financial statements and related
matters. Please contact Juan Grana at 202-551-6034 or Lauren Nguyen at
202-551-3642 with
any other questions.

 Sincerely,

 Division of
Corporation Finance
 Office of
Industrial Applications and
 Services
cc: Nathan Ajiashvili, Esq.
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