An 80-year-old white man underwent pylorus-preserving pancreaticoduodenectomy after presenting with obstructive jaundice and a dilated biliary tree on cholangiopancreatography. Histologic evaluation of the specimen revealed synchronous autoimmune pancreatitis (lymphoplasmacytic sclerosing pancreatitis) and infiltrating ductal adenocarcinoma of the pancreas. The mixed inflammatory infiltrate centered on the pancreatic ducts was associated with acinar loss, parenchymal fibrosis, and obliterative venulitis. Immunohistochemical labeling with an antibody to IgG4 revealed greater than 50 IgG4-positive plasma cells per high power field. Although not appreciated grossly, pancreatic intraepithelial neoplasia-3 and a neurotropic infiltrating poorly differentiated adenocarcinoma of the pancreas were also present. This case highlights the importance of carefully evaluating patients with autoimmune pancreatitis to rule out an underlying neoplasm and the importance of following those who were treated nonsurgically until the disease fully resolves.