Melanoma is a dangerous form of skin cancer arising from abnormal melanocytes. It accounts for only a small percentage of skin cancers, yet is responsible for the majority of deaths. The application of chromosomal microarray (CMA) with next-generation sequencing (NGS) could be a novel method for diagnosis, prognosis, and treatment of melanoma. Melanoma has non-random copy number changes and mutations. Copy number changes common in the diagnosis and prognosis of melanoma are loss of 1p, 6p, 6q, 7q, 9p, 10q and gain of 1q, 5p, 6, 6p, 6q, 7, 7p, 7q, 8, 8q, 11q, 12q. In order to determine the clinical utility of combining CMA and NGS, 30 cases sent to PathGroup were reviewed. All cases had at least one common copy number change. 28 cases (93.33%) had at least one targetable copy number change. The most common change was a loss of CDKN2A (9p21.3) in 26 cases (86.87%), which can be targeted by CDK4/6 inhibitors such as palbociclib. 28 cases were analyzed with NGS with 25 (89%) having a detectable mutation. The most common mutation was BRAF (predominantly V600E) mutation seen in 8 cases (32%), which can be targeted by RAS/RAF inhibitors such as trametinib and dabrafenib. 3 cases (10.71%) showed targetable genes by CMA when no mutation was seen. These data demonstrate the clinical utility of combining CMA and NGS in detecting copy number changes and mutations that can assist in diagnosis, prognosis, and treatment of melanoma.