CDKN2A gene functions as an important tumor suppressor via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. CDKN2A is a major high-risk susceptibility gene identified in melanoma. Somatic mutations of CDKN2A are reported in up to 19% and 20% of cutaneous and desmoplastic melanomas, respectively. Germline mutations have been reported in ~20-40% of families with melanoma. CDKN2A V126D mutation has been reported in numerous cases of familial melanoma and shown to be a loss-of-function mutation with reduced CDK4 binding. Correlation with other clinical and lab findings is necessary.