Cutaneous, acral and mucosal subtypes of melanoma (n=183) were evaluated by high coverage, whole-genome sequencing (WGS) in the largest such analysis to date. The heavily mutated landscape of coding and non-coding mutations in cutaneous melanoma displayed signatures of known and novel ultraviolet radiation mutagenesis. In marked contrast, acral and mucosal melanomas were dominated by structural changes and mutation signatures of unknown aetiology, not previously identified in melanoma. Further multinational studies will be needed to identify the preventable causative factors responsible for these tumours. The number of genes affected by recurrent mutations disrupting non-coding sequences was similar to that affected by likely driver mutations of coding sequences. Mutations affecting the TERT promoter were the most frequent of all, however neither they nor ATRX mutations, associated with the alternative telomere lengthening mechanism, were correlated with greater telomere length. Most melanomas had potentially actionable mutations, and most of these were in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways.