A number of autoimmune diseases predispose to the development of neoplasia. A particularly well-recognized association is the development of lymphoma in Sjögren's syndrome. Although this risk has been estimated to be 44 times that of the general population, few reliable prognostic indexes exist for individual patients. Recent advances in molecular biology have improved our understanding of Sjögren's syndrome and permitted better characterization of the generalized lymphoproliferation associated with the condition. This article reviews the histopathology of the major and minor salivary gland lesions of Sjögren's syndrome and discusses advances in molecular biology that have permitted more accurate prediction of lymphoma development in this group of patients.