Inclusion Criteria:

- ≥ 18 years of age

- Histologically confirmed classical HCL with one of the following:

- Intolerance to purine analogs

- Failure to achieve any response (CR or PR) to the initial purine analog-based therapy

- Relapse ≤ 2 years of purine analog-based therapy

- ≥ 2 relapses Histologic confirmation of diagnosis will be performed at MSKCC or a
participating site.

- Patients who meet the standard treatment initiation criteria, as defined by ANC ≤1.0,
Hgb ≤ 10.0 or PLT ≤100K

- ECOG performance status of 0-2

- Acceptable pre-study organ function during screening as defined as: Total bilirubin ≤
1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) ≤ 2.5x ULN, and serum creatinine ≤ 1.5x ULN

- Electrocardiogram (ECG) without evidence of clinically significant ventricular
arrhythmias or ischemia as determined by the investigator and a rate-corrected QT
interval (QTc, Bazett's formula) of < 480 msec.

- For women of childbearing potential, agreement to the use of two acceptable methods
of contraception, including one barrier method, during the study and for 6 months
after discontinuation of vemurafenib

- For men with female partners of childbearing potential, agreement to use a latex
condom and to advise their female partner to use an additional method of
contraception during the study and for 6 months after discontinuation of vemurafenib

- Negative serum pregnancy test within 7 days of commencement of treatment in
premenopausal women.

- Agreement not to donate blood or blood products during the study and for at least 6
months after discontinuation of vemurafenib; for male partners, agreement not to
donate sperm during the study and for at least 6 months after discontinuation of
vemurafenib

- Ability to understand and willingness to sign a written informed consent document.

- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures.

Exclusion Criteria:

- Pregnant or breast-feeding

- Have had chemotherapy (including purine analogs, rituximab, and other investigational
agents) within six weeks prior to entering the study

- Major surgery within 4 weeks prior to entering the study

- Invasive malignancy within the past 2 years prior to first study drug administration,
except for adequately treated (with curative intent) basal or squamous cell
carcinoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the
breast, in situ prostate cancer, or limited stage bladder cancer or other cancers
from which the patient has been disease-free for at least 2 years

- Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of
any type of gastrointestinal surgery that would preclude adequate absorption of study
drug

- Prior treatment with MEK or BRAF inhibitors

- Active HIV, hepatitis B and hepatitis C

- Patients with HCL variant (as defined by absence of expression of CD25 or absence of
BRAF V600E mutation)