Inclusion Criteria:

Patient MUST:

1. Have signed and dated written informed consent.
2. Be aged ≥ 18 years old at time of informed consent.
3. Have histologically proven Stage IIIc or IV malignant melanoma with documented progression during or following the most recent prior melanoma therapy.
4. Have measurable disease, defined as lesions that can be accurately measured in at least one dimension as > 20 mm with conventional techniques (CT) or > 10 mm with spiral CT scan or brain MRI.
5. Have failed at least 1 prior therapy for melanoma or refused first-line, standard therapy.
6. Have an ECOG performance status of 0 - 1.
7. Have a life expectancy, based on the Investigator's judgment, of > 3 months.
8. On screening ECG, have a QTc interval of < 450 ms.
9. If taking steroids, be on a dose that is stable for at least 5 days prior to the Imaging Dose.
10. Have recovered from the toxicity of all previous therapy prior to enrollment. If the patient has undergone recent major surgery, an interval of at least 3 weeks must have elapsed between the surgery and the date of the Imaging Dose.

11. Have acceptable laboratory results as follows:

    1. Hemoglobin ≥ 9g/dL
    2. ANC ≥ 1,500 mm3
    3. Platelet count ≥ 150,000 mm3
    4. PT <1.5 ULN
    5. PTT < 1.5 ULN
    6. Total Bilirubin < 2.0 mg/dL
    7. AST/ALT < or = 5 ULN
    8. Serum Creatinine < or = 2 mg/dL
12. Have a negative serum pregnancy test within 14 days of study drug administration, if female and of child bearing potential.
13. Agree to use an effective form of contraception to avoid pregnancy, if fertile (applicable to both male and female patients).
14. Agree to refrain from nursing, if female.

15. Be able to comply with treatment plan, study procedures, and follow-up examinations.

    If enrolled in the single site Sub-Study, patient MUST:

16. Have at least one accessible biopsy site and a second measurable target site per RECIST criteria.
17. Agree to pre-infusion and post-infusion biopsies of tumor lesions.

Exclusion Criteria:

Patient May Not:

1. Have a serious concurrent infection or medical illness which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety. Examples of medical illnesses include, but are not limited to, the following: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, known history of HIV, Hepatitis B or Hepatitis C infection, or psychiatric illness/social situation which would limit compliance with study requirements.
2. Have CNS metastases, unless, in the PI's judgment, the CNS involvement is stable and not likely to require further palliative therapy to the CNS during the course of the treatment protocol. If previous treatment has included radiotherapy, CNS disease should be stable at least 6 weeks from receipt of previous radiotherapy.
3. Have a prior malignancy with less than 3-year disease-free interval, except for adequately treated basal cell or squamous cell carcinoma of the skin, or in situ cancer of the cervix.
4. Have received radiation treatments < 6 weeks prior to first study drug administration (Imaging Dose).
5. Have previously received radiation to ≥ 25% red bone marrow.
6. Have received any cytotoxic chemotherapy, hormonal therapy, or immunotherapy, whether conventional or investigational, < 4 weeks prior to receiving the first study drug (Imaging Dose) administration in this study (6 weeks for mitomycin-C or nitrosoureas).
7. Have a history of pulmonary embolism within 1 year or deep venous thrombosis within six months of study enrollment.
8. Current or recent history of high-dose aspirin, warfarin, or heparin use (Aspirin < or = 81 mg/day, low-dose warfarin < 1 mg/day, or low-dose heparin for IV catheter patency is allowed).
9. Received investigational agents within 4 weeks prior to receiving the first study drug (Imaging Dose) administration in this study.
10. Have a history of allergic reactions attributed to compounds of similar chemical or biological composition to 131I-TM601 e.g. iodine or iodine-containing drugs.