BACKGROUND: Few studies have addressed prognostic markers and none has correlated molecular status and prognosis in vulvar melanomas. OBJECTIVES: To evaluate the clinicopathological features of 95 cases of vulvar melanoma. METHODS: p53, CD117, Ki-67, neurofibromin, brafv600e and nrasq61r immunostains, and molecular analyses by either targeted next-generation or direct sequencing, were performed on available archival materials. RESULTS: Molecular testing detected mutations in KIT (44%), BRAF (25%), NF1 (22%), TP53 (17%), NRAS (9%) and TERT promoter (9%). Co-mutation of KIT and NF1 and of KIT and NRAS were identified in two and one cases, respectively. KIT mutations were significantly associated with better progression-free survival in univariate analyses. In multivariate analyses CD117 expression was significantly associated with better progression-free survival. Tumour thickness was significantly associated with worse progression-free and overall survival, and perineural invasion significantly correlated with reduced melanoma-specific survival and reduced overall survival. Cases were from multiple centres and only a subset of samples was available for molecular testing. CONCLUSIONS: KIT mutations and CD117 overexpression are markers of better progression-free survival. In addition to its prognostic value, molecular testing may identify cases that might respond to targeted agents or immunotherapeutic approaches.