Sjögren’s syndrome (SS) is a complex autoimmune disease with multi-organ involvement. Its most serious complication is the development of non-Hodgkin lymphoma (NHL). In cohorts of unselected patients with long observation, this lifetime risk is estimated to be 5 to 15%, or approximately 20 times increased risk compared to the general population. Being able to identify patients prone to malignancy would significantly aid in the process of customised treatment and strategy for follow-up. Among the established predictors for lymphoma development in SS, we recognize recurrent or permanent swelling of major salivary glands (SG), lymphadenopathy, cryoglobulinemia, splenomegaly, low complement levels of C4 and C3, lymphopenia, skin vasculitis or palpable purpura, M-component in serum or urine, peripheral neuropathy, glomerulonephritis and elevated beta2-microglobulin. More recent suggestions include some genetic factors, CD4 lymphocytopenia, and ectopic germinal center-like structures in minor SG biopsies. Despite these predictors, there remains a need for defining algorithms for NHL screening and patient follow-up in SS.