The investigators want to learn to predict which tumors will respond to CVT chemotherapy. CVT is a combination of three drugs - cisplatin, vinblastine, and temozolomide. We and other investigators have used CVT in melanoma patients and found that tumors got significantly smaller in 30-40% of cases. In this study, the investigators want to get a precise idea of how many patients will respond to CVT. Also they want to test which genes in the tumor are turned on and which are turned off. We hope this will teach us to know in the future which tumors will respond to CVT.

Inclusion Criteria:

• Age ≥ 18 years
• Histologic proof of melanoma reviewed and confirmed at MSKCC
• Patients must have stage IV melanoma or recurrent stage IIIb or IIIc melanoma. Patients who are potentially respectable will be eligible.
• Measurable disease (RECIST criteria). Patients must have a tumor amenable to biopsy for oligonucleotide microarray analysis and for immunohistochemistry. A pre-treatment biopsy is required; a fine needle aspirate is not adequate.
• No prior cytotoxic chemotherapy for melanoma. Prior immunotherapy or anti-angiogenic therapy is allowed.
• No other concurrent chemotherapy, immunotherapy, or radiotherapy
• ECOG performance status ≤ 1
• Adequate organ function defined as follows: ANC >1500/mm3, Platelets >130,000/mm3, calculated creatinine clearance ≥60 ml/minute (Cockcroft & Gault).
• Adequate cardiac function to tolerate the hydration needed for cisplatin administration.

Exclusion Criteria:

• History of CNS metastases unless brain metastases have been resected or successfully treated with stereotactic radiosurgery and the patient has been free from CNS recurrence for 3 months.
• Uveal melanoma primary
• Patients who have had prior anti-CTLA4 monoclonal antibody treatment must have been off treatment for at least 4 months and have signs of progression of disease.
• Frequent vomiting or medical conditions that could interfere with oral medication intake
• Serious infection requiring antibiotics, or nonmalignant medical illnesses that are uncontrolled or whose control might be jeopardized by the complications of this therapy.
• History of HIV infection even if on HAART
• Immunosuppressive drugs
• High dose vitamins and herbs
• Other on-going investigational therapy, concurrent chemotherapy, immunotherapy or radiotherapy.