The symptoms of swelling of the submandibular salivary glands (SMSG) are unspecific and maybe encountered in various systemic disorders. Differential diagnostics of these diseases is difficult because of the similarity of their clinical manifestations. Furthermore, it is impossible to diagnose these manifestations using standard approaches. The authors propose the method for biopsy of submandibular salivary glands that markedly accelerates diagnostics and thereby provides an opportunity for thee arly treatment of SMSG swelling. The method makes possible the differential diagnostics between MALT lymphomas including the cases of Sjögren’s syndrome and Sjögren’s disease, IgG4-related sclerosing sialadentitis, AL-amyloidosis, sarcoidosis, sialadenosis, and other pathological conditions associated with the diffuse lesions in the salivary glands. In the majority of the cases, the morphological examination and immunohistochemcal studies of the salivary gland tissue are the only methods for the establishment of the definitive diagnosis.