So far, melanoma-specific antigens (such as Melan-A, or PMEL17 recognized by the HMB45 monoclonal antibody) are widely used for the immunochemical assessment of melanoma specimens, and S100β is considered a marker of relapse or hidden metastases, but its utility is under discussion and no molecular method to improve risk stratification is commonly used in the clinical practice. The gene discussed is S100B; the disease is melanoma.