BACKGROUND: Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis with a discrete pathophysiology, occasional diagnostic radiological findings, and characteristic histological features. Its etiology and pathogenesis are still under investigation, especially during the last decade. Another aspect of interest is the attempt to establish specific criteria for the differential diagnosis between autoimmune pancreatitis and pancreatic cancer, entities that are frequently indistinguishable.DATA SOURCES: An extensive search of the PubMed database was performed with emphasis on articles about the differential diagnosis between autoimmune pancreatitis and pancreatic cancer up to the present.RESULTS: The most interesting outcome of recent research is the theory that autoimmune pancreatitis and its various extra-pancreatic manifestations represent a systemic fibro-inflammatory process called IgG4-related systemic disease. The diagnostic criteria proposed by the Japanese Pancreatic Society, the more expanded HISORt criteria, the new definitions of histological types, and the new guidelines of the International Association of Pancreatology help to establish the diagnosis of the disease types.CONCLUSION: The valuable help of the proposed criteria for the differential diagnosis between autoimmune pancreatitis and pancreatic cancer may lead to avoidance of pointless surgical treatments and increased patient morbidity.