Clonal plasma cells residing within the bone marrow produce circulating monoclonal proteins that may subsequently lead to increased proliferation of dermal fibroblasts and excess mucin production. This pathologic process results in the myriad of depicted cutaneous and extracutaneous manifestations of scleromyxedema. Key cutaneous signs depicted include (a) leonine facies: deeply furrowed “lumpy” face with prominent superciliary arches resembling that of a lion, (b) the shar-pei sign: deep furrows in the skin of the back characteristic of the shar-pei breed of dog, and (c) the doughnut sign: induration of skin with central depression over proximal interphalangeal joint. Possible therapies include treatments directed against the plasma cell clone or the circulating monoclonal protein. H&E, hematoxylin and eosin; TGF-β, transforming growth factor-β; TNF-alpha, tumor necrosis factor-alpha. Joanna R. King (Mayo Clinic, Rochester) provided assistance to the authors in creating the figure; Julia S. Lehman (Mayo Clinic, Rochester) shared inlay histology images for the figure.