Inclusion Criteria:

1. Ability to provide informed consent.

2. Between 18 and 75 years of age.

3. Have a primary melanoma that is cutaneous (including head, neck, trunk, extremity,
scalp, palm, sole, subungual skin tissues).

4. Have clear margins following WLE.

5. ECOG performance status 0-1.

6. Life expectancy of at least 10 years from the time of diagnosis, not considering the
melanoma in question, as determined by the PI.

7. Willing to return to the MSLT-II center for follow up examinations and procedures as
outlined in the protocol.

8. Randomization and/or CLND (as appropriate to randomization arm) must be completed no
more than 120 days following the diagnostic biopsy of the primary melanoma.

9. Have a melanoma-related tumor-positive SN, determined by either of the following
methods:

1. Diagnosis of tumor-positive SN by MSLT-II center institutional pathologist by
either H&E or IHC (using S-100, Mart-1, and HMB-45).

2. Diagnosis of tumor-positive SN by RT-PCR analysis performed at JWCI, provided
the primary melanoma fits into one of the following categories:

- Breslow thickness of 1.20 mm or greater and Clark Level III

- Clark Level IV or V, regardless of Breslow thickness

- Ulceration, regardless of Breslow thickness or Clark level

Exclusion Criteria:

1. History of previous or concurrent (i.e., second primary) invasive melanoma.

2. Primary melanoma of the eye, ears, mucous membranes or internal viscera.

3. Physical, clinical, radiographic or pathologic evidence of satellite, in-transit,
regional, or distant metastatic disease.

4. Any additional solid tumor or hematologic malignancy during the past 5 years except
T1 skin lesions of squamous cell carcinoma, basal cell carcinoma, or uterine cervical
cancer.

5. Skin grafts, tissue transfers or flaps that have the potential to alter the lymphatic
drainage pattern from the primary melanoma to a LN basin.

6. Allergy to vital blue dye or any radiocolloid.

7. Inability to localize 1-2 SN drainage basins via LM (e.g., no basins found, more than
2 basins found, proximity of the primary melanoma to the regional draining basin,
etc.)

8. CLNDs or SLs (before evaluation of the current melanoma) that may have altered the
lymphatic drainage pattern from the primary cutaneous melanoma to a potential LN
basin.

9. Organic brain syndrome or significant impairment of basal cognitive function or any
psychiatric disorder that might preclude participation in the full protocol, or be
exacerbated by therapy (e.g., severe depression).

10. Melanoma-related operative procedures not corresponding to criteria described in the
protocol.

11. Primary or secondary immune deficiencies or known significant autoimmune disease.

12. History of organ transplantation.

13. Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at any
time during study participation or within 6 months prior to enrollment.

14. Pregnant or lactating women.

15. Participation in concurrent experimental protocols or alternative therapies that
might confound the analysis of this trial. Adjuvant therapy protocols after
recurrence are acceptable.