The observation of the bona fide TSGs affected by promoter hypermethylation in CMM suggests that these molecules, e.g., TCF21, SOCS, RUNX, RASSF6, RASSFA, RARβ, MAPK13, H- and E-cadherin and AGTR, are a candidate for the design of new therapeutic strategies for human melanoma. The gene discussed is TCF21; the disease is melanoma.