All 23 melanoma cell lines evaluated resulted in wild-type configuration for the ligands SHH, DHH, and IHH, the repressors PTCH1, PTCH2, and SUFU, the effectors SMO, GLI1, GLI2, and GLI3 genes, indicating that deregulation of the Hh intracellular signaling might arise from mechanisms not involving mutational events. The gene discussed is SMO; the disease is melanoma.