In 2009, Leachman et al. proposed that, in regions with a moderate to high incidence of melanoma, the higher rates of CDKN2A positivity is reached in individuals abiding the rule of 3: cases with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family [31]. This evidence concerns the gene CDKN2A and melanoma.