Overproduction of a vascular endothelial growth factor secreted by neoplastic cells in some plasma cell neoplasms is postulated to be responsible for the syndrome of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes and the rarer syndrome of adenopathy and extensive skin patch overlying a plasmacytoma. The authors present a case of a 57-year-old man who presented with an erythematous left flank skin patch and subsequent discovery of an underlying 10th rib plasmacytoma with lambda light chain restriction. The tumor was strongly positive for CD31, a marker known to be involved in angiogenesis and cell adhesion. Immunohistochemical studies were initially confounding and later shown to be due to the effects of decalcification procedures. The authors discuss the natural history of this unusual entity and the diagnostic challenges in evaluating this lesion. The authors finally postulate whether strong CD31 expression could be related to paraneoplastic phenomena associated with some plasma cell lesions.