We demonstrate here that malignant melanoma represents a potentially responsive target to vitamin D. Although mutational analysis of VDR gene, CYP27A1, CYP27B1 and CYP24 A1 genes may be required before to consider a vitamin D treatment, relevant mutational events, which impair melanoma cells sensitivity to D-hormone, seem to be sporadic. The gene discussed is CYP27A1; the disease is melanoma.