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. The gene discussed is CFL2; the disease is melanoma.