Oncogenomic studies have revealed genetic alterations that affect tumor progression. Included amongst these alterations are focal and broad recurrent copy number variations (CNVs). Identifying driver genes, which are responsible for disease progression, in broad CNVs is challenging as these regions harbor many bystander passenger genes that are altered due to their proximity to drivers. To enrich for driver genes in regions of CNV we performed comparative oncogenomics with human and zebrafish melanomas. Coupling this approach with transcriptome analyses, we identified the BMP factor GDF6 as a novel melanoma oncogene. GDF6 is specifically expressed in melanomas and not melanocytes, and its knockdown led to melanoma cell death. Enforced expression of GDF6 promoted melanoma growth in an autochthonous zebrafish model as well as in mouse xenografts. Genetic epistasis analysis indicated that GDF6 acts via SMAD1 to aid in melanoma cell survival. Transcriptome analyses of melanoma cells with GDF6/BMP modulation found that a major role of GDF6 is to regulate expression of genes important in neural crest development. Indeed, GDF6 and its orthologs are expressed in the neural crest, where they regulate cell survival and fate specification. Mechanistic analyses determined that GDF6 acts via suppression of the neural crest factor SOX9, which is an established pro-apoptotic factor in melanomas. To extend the relevance of these findings to the clinic we analyzed melanoma patient samples and found that nearly 80% of human melanomas express high levels of GDF6 and have an active BMP pathway. Furthermore, GDF6 expression correlated with poor overall survival of melanoma patients. We found that treatment with a BMP pathway small molecule inhibitor, DMH1, attenuated melanoma growth in mouse xenografts. Our findings have established that GDF6-dependent BMP signaling endows melanoma cells with a pro-survival, neural crest identity. Additionally, our results highlight GDF6 and BMP pathway components as novel targets for therapeutic intervention of melanomas.