Here, we provide an update on the molecular background of melanoma, including a description of four already established molecular subtypes: BRAF+, NRAS+, NF1+, and triple WT, as well as relatively new NGS-derived melanoma genes such as PREX2, ERBB4, PPP6C, FBXW7, PIK3CA, and IDH1. We also present a comparison of genomic profiles obtained in recent years with a focus on the most common melanoma genes. This evidence concerns the gene PPP6C and melanoma.