Sjögren's syndrome (SS) is a chronic autoimmune disease that involves primarily the exocrine glands and results in their functional impairment. The disease may occur alone (primary SS, pSS) or in association with other autoimmune diseases, such as rheumatoid arthritis (secondary SS, sSS). Although the clinical manifestations of pSS patients are mainly those of an autoimmune exocrinopathy, 40% to 50% of patients develop extraglandular disease, which may be manifested either by epithelial lymphocytic invasion of lung, liver, or kidney (resulting in interstitial nephritis) or by skin vasculitis, peripheral neuropathy, glomerulonephritis, and low C4 levels, conditions which represent an immune-complex mediated disease. Patients belonging to the latter category, inferring a high risk for development of non-Hodgkin's lymphoma, by default have a worse prognosis with higher mortality rates. In this review, the role of several factors involved in mortality of pSS, as well as markers predictive for lymphoma development are discussed.