Sjögren's syndrome (SS) is a chronic auto-immune exocrinopathy, especially affecting the lacrimal and salivary glands. The aim of this study is to improve the diagnostic possibilities of the sublabial salivary gland (SSG) biopsy. The SSG biopsies of 19 patients with SS and 65 healthy control subjects were used in a quantitative immunohistologic and histomorphometric study. Statistical analysis of the immunohistochemical data resulted in a diagnostic criterion, which is based on the percentages of IgA- and IgG-containing plasma cells. Statistical analysis of 3 immunohistologic and 6 histomorphometric features resulted in a combined immunohistologic and histomorphometric criterion, which is based on 2 immunohistologic parameters (the percentages IgA- and IgG-containing plasma cells) and 3 histomorphometric parameters (the volume percentages of acini, intralobular ducts and diffuse lymphoplasmacytic infiltrate). The immunohistologic diagnostic criterion has a specificity of 95.4%, a sensitivity of 100% and an overall percentage of misclassification of 3.6%. The combined diagnostic criterion has a specificity of 98.5%, a sensitivity of 100% and an overall percentages of misclassification of 1.2%. Furthermore it reduces the number of false positive diagnoses with a factor 6 from 9% to 1.5%.