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Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects exocrine glands. A diagnosis of SS in its early stages has a potential clinical relevance, but it is difficult and cannot be made solely on clinical grounds. Several sets of diagnostic criteria have been proposed, but none has met with a general consensus. Minor salivary gland has been judged to be the "gold standard" for the diagnosis of SS. However, it is a painful procedure and has a small but significant proportion of both false positive and false negative results. The aim of our study was to develop a simple mathematical score that uses clinical and laboratory variables for diagnosing SS, thereby reducing the need of minor salivary gland. The following variables were included in the model: ANA, SS-A/SS-B, Schirmer's Test/BUT, C3/C4, serum gammaglobulin levels. One hundred consecutive individuals reporting clinical syndromes consistent with a sicca syndrome were included in the study. The application of our multifactorial mathematical model has shown a high predictive value for SS vs controls or vs patients with other autoimmune disorders (Sensitivity 93%, Specificity 100%), with an estimated minor salivary gland reduction of 77%. We conclude that our mathematical model can be considered a useful non-invasive approach for diagnosing Sjogren's Syndrome and recommend its validation on a larger scale.