Over the last decades several drugs have been approved for IIIC-IV unresectable/metastatic melanoma, including multiple combinations of BRAF/MEK inhibitors (dabrafenib + trametinib, vemurafenib + cobimetinib and encorafenib + binimetinib) and immunotherapeutic agents, such as nivolumab, pembrolizumab and ipilimumab (Table 2). The gene discussed is BRAF; the disease is metastatic melanoma.