Inactivating variants in NF1, the most frequently mutated gene in melanoma after BRAF/NRAS/TP53, being reported in 10–15% of cases, were described in up to 46% of wild-type BRAF and RAS melanomas, in particular in male, older or chronically sun-exposed patients, and in copresence of mutations in RASopathy genes, e.g., PTPN11 and RASA2, that enhance its role in melanomagenesis, besides the RAS missing inhibition (Krauthammer et al., 2015). This evidence concerns the gene BRAF and RASopathy.