Objectives: To evaluate potential systemic, oral and salivary distinguishing characteristics for patients with primary Sjögren’s syndrome (pSS) from non-primary Sjögren’s syndrome (non-pSS) patients. Methods: Forty patients referred for diagnosis of pSS underwent an interview including exocrine and non-exocrine symptoms and manifestations, assessment of fatigue using the Multidimensional Fatigue Inventory MFI-20, an oral (dental and periodontal status) and ocular (Schirmer’s test, tear break-up time and Lissamine green staining) examination, measurements of unstimulated (UWS) and chewing-stimulated whole saliva (SWS) flow rates, a labial salivary gland biopsy and test for serum autoantibodies. Results: Fourteen females and one male (aged 57±12 years) fulfilled the American-European Consensus Classification Criteria, whereas 22 females and 3 males (aged 55±14 years) did not. No significant differences were found in symptoms of oral and ocular dryness, concomitant systemic diseases, no. of prescribed medication, mean score of decayed-missed-filled-teeth, levels of plaque, gingival inflammation and probing depth. However, patients with pSS had lower UWS (0.04±0.06 ml/min vs. 0.13±0.12 ml/min, P=0.026) and SWS (0.47±0.50 ml/min vs. 0.84±0.60 ml/min, P=0.038) flow rates, and higher fatigue scores (P=0.046). Lymphocytic infiltration, i.e. with focus score ≥1,was found in the salivary gland biopsies from 47% of the patients with pSS and in none of those from non-pSS patients (mean focus score 2.3±4.0 vs. 0.02±0.06, P<0.001). In the remaining 53% of pSS patients, the salivary gland tissue was characterized by atrophy, fibrosis and diffuse inflammation. All patients with pSS had elevated levels of circulating anti-Ro/SSA serum autoantibodies as compared to 28% in the non-pSS group (P<0.001). Conclusion: Our preliminary findings indicate that oral, ocular and systemic symptoms and manifestations are poor distinguishing characteristics. A salivary gland biopsy with a focus score > 1 had a high predictive value for the diagnosis of pSS. Presence of anti-Ro/SSA autoantibodies had a high sensitivity for pSS but a lower specificity due to several false positive serum samples. Our on-going study includes a larger cohort to substantiate our preliminary findings and discover more specific biomarkers for pSS.