Labial salivary gland biopsy (LSGB) is a minimally invasive and safe surgical procedure performed in the diagnosis and monitoring of selected diseases such as Sjögren’s syndrome (SS), sarcoidosis, and amyloidosis. The aim of this study is to present the main possibilities and indications for the usefulness of LSGB in these diseases, their histopathological criteria, and the main advantages and limitations. Histopathological confirmation of SS is based on the presence of lymphocytic infiltrates, known as focal lymphocytic sialadenitis (FLS). FLS refers to the histopathological pattern of the presence of one or more foci in the biopsies, while the tissue surrounding the foci is composed mainly of unaffected parenchyma. A focus is defined as an aggregate of ≥ 50 lymphocytes, and the focus score (FS) is the total number of foci per 4 mm² of salivary gland tissue. FLS should be distinguished from other types of sialadenitis such as nonspecific chronic sialadenitis, sclerosing chronic sialadenitis, granulomatous inflammation, and lymphomas.