Recurrent loss of SPRED1, a negative regulator of the mitogen-associated protein kinase (MAPK) pathway which acts by recruiting NF1 to the plasmatic membrane, has been found in 37% of 47 patients with mucosal melanomas, mostly of anorectal and vulvovaginal origin: this molecular alteration was mutually exclusive with NF1 mutations, which were found in 12% of patients [17]. The gene discussed is SPRED1; the disease is melanoma.