To study if a targeted gene expression profile of RNA, similar to the NETest, can be isolated from the peripheral blood of patients with melanoma, to identify active disease, provide an assessment of treatment responses, or predict risk of relapse, in conjunction with standard clinical assessment and imaging.

• Evaluate the diagnostic efficacy of a circulating melanoma gene signature in pathologically verified Stage III melanoma at diagnosis (biopsy-proven lymph node positive) and compare this to LDH as a biomarker.
• Evaluate the diagnostic efficacy of a circulating melanoma gene signature in pathologically verified Stage IV melanoma (including pre-surgery patients as well as those on either targeted or immunotherapy) and compare this to LDH as a biomarker.
• Define the assay metrics for sensitivity and specificity in diagnosis in Stage III and IV tumors.
• Monitor molecular signature levels in blood to assess efficacy of this tool as compared to imaging or other biomarkers to define disease progression or treatment responses in Stage III and IV treated patients.

Inclusion Criteria:

1. Age > 18 years
2. Primary melanoma > 1 mm in Breslow depth
3. Stage III or IV disease as determined either by sentinel node biopsy, biopsy of clinically enlarged lymph nodes, and/or imaging. If stage IV, must have tissue biopsy confirming presence of stage IV melanoma

Exclusion Criteria:

1. Pregnant patients
2. Contraindication to contrasted imaging (due to allergy or renal insufficiency)
3. Serum PCV <30%

Adults with a diagnosis of stage III or IV melanoma.