One of the best-recognized cutaneous manifestations of internal disease includes the skin changes seen in endocrine diseases. Cutaneous manifestations of internal disease can also be seen with certain neoplastic processes. Metabolic disturbances in zinc, lipid metabolism, or increased amino acid catabolism can result in zinc-responsive dermatosis, cutaneous xanthomas, and superficial necrolytic dermatitis, respectively. Certain infectious diseases can result in skin lesions that may provide visual clues but also critical diagnostic information if the skin is biopsied and cultured. Recognizing those skin changes that are clinical markers for internal disease can expedite the diagnosis and timely management of several systemic diseases.