Paraneoplastic pemphigus (PNP) is a rare but severe multiorgan autoimmune disease that occurs in the presence of an underlying neoplasm. It is clinically characterized by a painful oral stomatitis, and a range of skin eruptions. In PNP, autoantibodies are directed against the intracellular desmosomal and hemidesmosomal plaque proteins of the plakin family: envoplakin, periplakin, desmoplakin, BP230 and plectin. In addition, the desmosomal proteins desmoglein (Dsg) 3 and less frequently Dsg 1 are targeted, as well as the protease inhibitor alpha-2-macroglobulin-like antigen-1 (A2ML1).(1-4) Diagnosing PNP largely depends on the demonstration of these autoantibodies. Immunoblotting and immunoprecipitation are sensitive and specific methods to detect these circulating antibodies. This article is protected by copyright. All rights reserved.