Melanoma of unknown primary (MUP) is an unusual phenomena whereby a patient will present with metastatic melanoma, but upon clinical examination the original primary site is never identified. Currently there is minimal evidence to explain their mechanism of development. To address this issue, we have compiled exome sequencing data on 33 MUP (11 early passage cell lines in addition to 22 tumours from publically available datasets) with mutation profiling on an independent panel of 92 FFPE and fresh frozen MUP screening for frequently occuring hotspot mutations in genes including BRAF, NRAS, KIT, GNAQ and GNA11. The majority of MUP exhibited a high somatic mutation rate and high ratio of C>T/G>A transitions, indicative of a carcinogenic UV damage signature. Mutation profiling revealed a high rate of BRAF (45 of 103, 43.7%) and NRAS (32 of 103, 31.1%) mutation with a distinct lack of mutations associated with non-cutaneous melanomas (KIT, GNAQ, GNA11). Our results indicate that MUP have a mutation profile consistent to that of cutaneous sun exposed melanomas; this data suggests a significant proportion of MUP arise from regressed or unrecognized primary cutaneous melanomas or through de novo development in sentinal lymph nodes from migrating nevus cells.