The primary goal of this study is to determine if people with metastatic melanoma who receive Heat Shock Protein-Peptide Complex - 96 (HSPPC-96 or Oncophage) after surgery live longer than people who may or may not have surgery but who receive conventional chemotherapy including IL-2/DTIC. A second goal is to determine the safety and frequency of side effects in subjects who receive therapy with HSPPC-96.

Primary Objective:

• To determine whether subjects with stage IV melanoma randomized to HSPPC-96 have longer survival than subjects randomized to physician's choice including interleukin-2 and/or dacarbazine/temozolomide and/or complete tumor resection.

Secondary Objective:

• To determine frequency of adverse events in subjects randomized to HSPPC-96.

Eligibility Assessment:

(The following assessments must be obtained within three weeks prior to randomization into the study)

• Medical history and physical examination (including EGOG score, evidence of immunosuppression);
• CT/MRI of the chest, abdomen and pelvis;
• Clinical examination;
• CT/MRI of the brain;
• Complete Blood Count with differential including platelets;
• Electrolytes (Na, Cl, K, HCO3, Ca, Mg, PO4);
• Renal function tests (BUN and creatinine);
• Liver function tests (bilirubin, AST, ALT);
• Serum pregnancy test for all women of childbearing potential.

Inclusion Criteria:

• Stage IV Melanoma (AJCC);
• No prior therapy for stage IV melanoma;
• No prior therapy with interleukin-2 and/or dacarbazine/temozolomide within the past 12 months prior to study entry;
• Candidate for surgical resection of some/all sites of melanoma and expected to obtain greater tan or equal to 7 grams of viable cancer tissue (in aggregate), which is equivalent to a greater than or equal to 2 cm lesion on CT/MRI or clinical examination;
• No brain metastases;
• ECOG score 0 or 1;
• Adequate cardiac function;
• Adequate hematopoietic, liver and renal function;
• Female subjects of child-bearing potential must agree to use contraception during the study
• Signed written informed consent.

Exclusion Criteria:

• Mucosal or ocular melanomas;
• Other malignancies treated within the last five years, except in situ cervix carcinoma or non-melanoma skin cancer;
• Primary or secondary immunodeficiency, in the opinion of the investigator (including immunosuppressive disease, or use of systemic corticosteroids or other immunosuppressive medications);
• Prior splenectomy;
• Uncontrolled infection or other serious medical illnesses;
• Women who are pregnant or breast-feeding;
• Subjects participating in any other studies requiring administration of an investigational drug/biologic agent.