Inclusion Criteria:

1. Willing and able give written informed consent.

2. Previously untreated and histologically confirmed Stage III (unresectable) or Stage
IV melanoma. Adjuvant interferon is acceptable however.

3. Subjects with asymptomatic brain metastases are eligible. (Systemic steroids should
be avoided if possible, or the subject should be stable on the lowest clinically
effective dose of steroids as they may interfere with the activity of ipilimumab if
administered at the time of the first ipilimumab dose.)

4. Must be at least 28 days since treatment with surgery or radiation, or immunotherapy
(IFN-alpha), and recovered from any clinically significant toxicity experienced
during treatment. Palliative radiation therapy outside of the brain or therapeutic
radiation to the brain after the subject's condition is stabilized and steroid
decreased to the lowest fixed dose possible does not require the 28- day waiting
period.

5. Easter Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

6. Life expectancy of more than 16 weeks.

7. Subjects must have the complete set of baseline (screening/baseline) radiographic
images, including but not limited to brain, chest, abdomen, pelvis, and bone scans.
The images can be accepted if obtained 6 weeks before initiation of ipilimumab.

8. Required values for initial laboratory tests: WBC > 2000/uL; ANC > 1000/uL; Platelets
> 100 x 103/uL; Hemoglobin > 9 g/dL (> 80 g/L; may be transfused); Creatinine < 2.0 x
ULN; AST/ALT < 2.5 x ULN for patients without liver metastasis, > 5 times for liver
metastases; Bilirubin > 2.0 x ULN, (except patients with Gilber's Syndrome, who must
have a total bilirubin less than 3.0 mg/dL); INR > 1.3

9. No active or chronic infection HIV, Hepatitis B, or Hepatitis C.

10. Men and women, greater or equal to 18 years of age.

Exclusion Criteria:

1. Sex and Reproductive Status: a) WOCBP who are unwilling or unable to use an
acceptable method to avoid pregnancy for the entire study and for up to 8 weeks after
the last dose of investigational product. b) WOCBP using a prohibited contraceptive
method. c) Women who are pregnant or breastfeeding. D) Women with a positive
pregnancy test on enrollment or before investigational product administration.

2. Target Disease Exceptions: a) Subjects on any other systemic therapy for cancer,
including any other experimental treatment. b) Prior treatment with an anti- CTLA-4
antibody if treatment failure was due to irAEs. If a subject was discontinued from
the prior anti-CTLA-4 treatment due to an AE or SAE, regardless of the type of event,
that discontinuation constitutes an exclusion criterion. If irAEs were serious enough
to require a subject's withdrawal from prior treatment, the subject should be
excluded from this study. c) Prior treatment with
chemotherapy/biochemotherapy/immunotherapy for systemic disease for melanoma.

3. Primary ocular and mucosal melanomas are not allowed.

4. Medical History and Concurrent Diseases: a) Autoimmune disease: subjects with a
documented history of inflammatory bowel disease, including ulcerative colitis and
Crohn's disease are excluded from this study as are subjects with a history of
symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis
[scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's
Granulomatosis]). Subjects with motor neuropathy considered of autoimmune origin
(e.g., Guillain-Barre Syndrome and Myasthenia Gravis) are excluded from this study.
b) Any subject who has a life-threatening condition that requires high-dose
immunosuppressant(s). c) Presence of known hepatitis B or hepatitis C infection,
regardless of control on antiviral therapy. d) Subjects with melanoma who have
another active, concurrent, malignant disease with the exception of subjects with
adequately treated basal or squamous cell skin cancer, superficial bladder cancer, or
carcinoma in situ of the cervix.

5. Other Exclusion Criteria: a) Prisoners or subjects who are involuntarily
incarcerated. b) Subjects who are compulsorily detained fro treatment of either a
psychiatric or physical (e.g., infectious disease) illness. c) Any underlying medical
or psychiatric condition that, in the opinion of the investigator, could make the
administration of ipilimumab hazardous or could obscure the interpretation of adverse
events. d) Any non-oncology vaccine therapy used for prevention of infectious
diseases for up to 4 weeks before or after any dose of ipilimumab, with the
exceptions of amantadine and flumadine.

6. Any acute or chronic treatment with warfarin or antiplatelet agent (aspirin is
allowed up tot a dose of 300 mg daily) including clopidogrel. Heparin, low molecular
weight heparin, any heparinoid are allowed after appropriate cessation (usually 24
hours).

7. Any known or suspected bleeding diathesis on the basis or personal or family history
(including diagnoses of von Willebrands disease or other familial factor deficiency).

8. The risk of the excision involves a significant risk of morbidity or mortality due to
its size, location or vascularity (at the discretion of the principal investigators).