This is the first study that investigates the activity of 17-aminogeldanamycin on the p65/NF-κB program in melanoma cell lines of genetically different subtypes, BRAF and RAS. Our report indicates that 17-aminogeldanamycin can counteract the effects of NF-κB activity mediated by NF-κB-dependent genes, encoding proteins involved in cell proliferation, invasion, and angiogenesis. This evidence concerns the gene RELA and melanoma.