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Identication of the properties of inheritance in hereditary melanoma was greatly accom­plished by Lynch etal. [37] in the early 1980s. Segregation analysis performed by the authors supported the FAMMM syndrome as an autoso­mal dominantly inherited syndrome that displays variable expressivity and reduced penetrance. Phenotypic variations such as cancers other than CMM noted in the FAMMM syndrome also led to identication of an association with pancreatic cancer by Lynch and Fusaro in 1991 [38]. Kaufman etal. described Melanoma Astrocytoma Syndrome (MAS) after identifying concurrent familial CMMs and nervous system tumors in 1993 [39]. Since 1997, the Melanoma Genetics Consortium, GenoMEL, comprised of research­ers worldwide, has been actively working on the genetics of familial CMM.Studies have shown that carrying inherited germline mutations in par­ticular cell cycle regulatory genes such as cyclin­dependent kinase 4 (CDK4) gene on chromosome 12q14 [40, 41] or the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene on chromosome 9p21 [42, 43] are considered to be major risk fac­tors for familial melanoma. The frequency of CDKN2A mutations is more common than CDK4 mutations (20–40% versus 2%) in melanoma­prone families [8] and the variable penetrance of these mutations is known to be modied by envi­ronmental factors (e.g., geographic location and sun exposure patterns) [44, 45], melanoma asso­ciated phenotypes and coinheritance of several