The immunohistochemical panel should include, in addition to cytokeratins and mesothelial markers, a series of mesenchymal markers, such as desmin, S-100, myogenin, STAT6, SS18-SSX, CD34, ERG, CD31, and FLI1, and melanoma markers, like SOX10, HMB45, and Melan A. The choice of the most appropriate panel obviously depends on the morphological features of the lesion in order to avoid unnecessary and sometimes confusing immunostaining. The gene discussed is DES; the disease is melanoma.