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Familial atypical multiple mole melanoma (FAMMM) syndrome is an autosomal dominant disorder with variable incomplete penetrance of the clinical phenotypes. Pathogenesis of this syndrome has not been fully investigated. Across multiple studies, germline mutations in the INK4a antioncogene encoding p16 protein were found on average in approximately 40% of the FAMMM syndrome. Patients with the FAMMM syndrome are genetically loaded with an increased risk of developing melanoma and other malignant neoplasms, for example, a pancreatic cancer. Melanoma can develop from numerous atypical moles as well as de novo. A proper diagnosis of the syndrome and early application of prophylactics decreases the risk of neoplastic transformation of melanocytes.