Sjögren's syndrome (SS) is an autoimmune systemic disease characterized by B-cell lymphoproliferation and an increased risk of B-cell non-Hodgkin lymphoma (NHL) development, mainly of the mucosa-associated lymphoid tissue (MALT) type, which impacts survival and mortality. MALT lymphoma arises from chronic inflamed tissues through a multistep process in which a local, chronic, antigenic stimulation, together with a predisposing genetic background and with additional proliferative stimuli provided by the local molecular and cellular milieu of ectopic lymphoid glandular tissue, allows the emergence of B-cell clonal expansion and its possible evolution into overt malignancy. A complete assessment of SS always includes salivary gland biopsy. Imaging may be helpful for a noninvasive assessment of lymphoproliferation but it cannot substitute biopsy. New therapeutic B-cell targeting strategies are emerging to treat SS-related lymphoproliferation, ie, SS itself.