Two cytokines have been approved by the Food and Drug Administration (FDA) for melanoma treatment as single agent: high doses of IL-2 for metastatic melanoma and IFN-α for the adjuvant therapy of Stage III melanoma based on the results obtained in clinical trials using high doses of IL-2 in metastatic melanoma patients (81) and IFN-α that demonstrated a significant benefit in relapse-free and overall survival of high-risk melanoma patients (82). This evidence concerns the gene IL2 and melanoma.