Objective: Sjogren's syndrome (SS) is an autoimmune disease involving primarily the salivary and lacrimal glands (“sicca” symptoms) with extraglandular features including joint and nervous system involvement. In patients with a questionable diagnosis of SS but severe extraglandular symptoms, a lip biopsy is often performed to firmly establish the diagnosis of SS. This study was undertaken to identify areas of uncertainty regarding the accuracy of biopsy interpretation and the diagnostic benefits of the procedure.

Study Design: Retrospective review of clinical and pathologic data.

Methods: Clinical data from 47 patients referred to the otolaryngology–head and neck surgery service for lip biopsy were reviewed. Archival pathologic specimens were scored using the currently accepted grading system.

Results: The grading system was incorrectly applied during initial interpretation of 45% (n = 21) of specimens. This resulted in five (10%) pathologic misdiagnoses and 16 (34%) nondiagnoses. On re‐interpreting the specimens with consistent application of the grading system, 62% (n = 29) of the biopsies were definitely positive, and 36% (n = 17) were negative. Neither positive serology nor the presence of sicca symptoms predicted a positive biopsy (likelihood ratio = 0.95 and 0.96, respectively). Lip biopsy guided treatment in at least 65% (n = 31) of patients but was ignored in the presence of other clinical findings in 17% (n = 8) of patients.

Conclusions: Consistent application of the grading system is essential in avoiding incorrect diagnosis and aiding clinical decisions. However, not all patients undergoing lip biopsy will derive diagnostic benefit from the procedure. In this series, clinical symptoms and serology did not predict positive lip biopsy.