Despite recent advances in targeted and immune-based therapies, advanced stage melanoma remains a clinical challenge with a poor prognosis. Understanding the genes and cellular processes that drive progression and metastasis is critical for identifying new therapeutic strategies. Rab GTPases are increasingly being implicated in cancer progression. Here, we found that the GTPase RAB27A was overexpressed in a subset of melanomas, which correlated with poor patient survival. Loss of RAB27A expression in melanoma cell lines inhibited 3D spheroid invasion and cell motility in vitro, and spontaneous metastasis in vivo. The reduced invasion phenotype was rescued by RAB27A-replete exosomes, indicating that exosomes drive RAB27A-mediated invasion. Furthermore, while RAB27A loss did not alter the number of exosomes secreted, it did change exosome morphology and the abundance of exosomal proteins associated with cancer cell migration and metastasis. Our data indicate that RAB27A tumour dependency only occurs in melanomas with relatively high levels of RAB27A expression. RAB27A tumour-dependency may also be largely restricted to melanoma, given that RAB27A protein has been shown to be enriched in melanoma cell lines compared to cell lines of other cancer types, and The Human Protein Atlas indicates that RAB27A expression is higher in melanoma compared to other cancers. Here we have highlighted the role of RAB27A in promoting exosome-mediated invasion and metastasis in melanoma. Our findings suggest that RAB27A is a key cancer regulator as well as a potential prognostic marker and therapeutic target in melanoma.