The United States Food and Drug Administration (FDA) approval of the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab in 2011 and the anti-programmed cell death protein 1 (PD-1) antibodies nivolumab and pembrolizumab in 2014 has radically changed the systemic treatment of metastatic melanoma and significantly improved its clinical outcome. This evidence concerns the gene CTLA4 and metastatic melanoma.