The p16INK4a protein, encoded by the CDKN2A gene (locus 9p21), plays an important role in regulating cell cycle phase transitions; several studies performing analyses on melanoma samples reported a methylation frequency in the CDKN2A promoter ranging from 5% to 27% and a significant overrepresentation in NRAS-mutated samples [26,27,28,29]. The gene discussed is NRAS; the disease is melanoma.