Nine alterations in eight genes of our cohort showed a statistically significant difference in frequency compared to the population databases (CYP1B1:p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F) which suggests they may have a potential role in affecting melanoma susceptibility. The gene discussed is POLE; the disease is melanoma.