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 the major high-risk susceptibility gene identified in melanoma. Somatic mutations of CDKN2A are reported in up to 19% and 20% of cutaneous and desmoplastic melanoma, respectively. Germline mutations have been reported in ~20-40% of families with melanoma. Correlation with other clinical and lab findings is necessary.