In conclusion, whatever the inhibitory mechanism, the results of the current study suggest that Rottlerin may offer a promising mono- or combined-therapeutic approach for a subpopulation of melanomas with constitutively active Ras/Raf mutants, cyclin D1 overexpression, and high NF-κB activity, for which a limited number of effective drugs are currently available. Here, NFKB1 is linked to melanoma.