Background: Ocular cicatricial pemphigoid is a chronic, progressive, autoimmune disease that scars mucous membranes and may lead to blindness. It is of critical importance to be able to make the diagnosis as early as possible to allow early treatment. Conjunctival biopsy facilitates the early diagnosis of this condition. Materials and Methods: Conjunctival biopsy results of 166 consecutive patients seen over a 7-year period, in whom the diagnosis of ocular cicatricial pemphigoid was considered, were reviewed. Results: One hundred twenty-one patients ultimately received a diagnosis of ocular cicatricial pemphigoid. Immunofluorescence studies demonstrated characteristic deposition of immunoreactants at the epithelial basement membrane zone in 63 patients (sensitivity = 52%). When immunofluorescent-negative or inconclusive biopsies were processed further using an immunoperoxidase technique an additional 37 diagnoses were made. This represented an increase in sensitivity from 52% with immunofluorescence only to 83% with the addition of the immunoperoxidase technique. Conclusion: The routine use of the immunoperoxidase technique in immunofluorescent-negative biopsies, allied with appropriate harvesting and handling of biopsied conjunctiva, should significantly increase the diagnostic yield in patients with clinically suspect ocular cicatricial pemphigoid.