We here described a stage-specific melanoma pro-invasive feature acquired from acid pH exposure, and exerted through exosomes enriched in HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1 genes, that were statistically related to melanoma patients poor prognosis. This evidence concerns the gene HSPA5 and melanoma.