Objective Aims of this study were to test the efficacy of anti‐BP180‐NC160 ELISA in the diagnosis of oral pemphigoid compared to the gold standard, represented by direct immunofluorescence and pathological examination, to correlate the antibody titers with the severity of the disease and the demographical data. Materials and Methods Patients with a suspect of oral pemphigoid were enrolled and underwent biopsy and sera collection both, in order to perform histopathological examination, direct immunofluorescence and ELISA. The test outcomes were compared, and ELISA sensitivity, specificity, accuracy, and negative and positive predictive values were calculated. Results ELISA showed good specificity (83.3%), while sensitivity was only 50%. A moderate correlation between antibody titers and disease severity was recorded. Conclusions Mucomembranous Pemphigoid is an autoimmune autoantibody‐mediated blistering disease, often affecting exclusively the oral mucosa. Currently, the biopsy is required to diagnose this disease, but serological tests are also commonly employed during clinical practice as adjunctive tools. BP180‐NC160 ELISA should be considered an ancillary diagnostic test in course of oral pemphigoid; direct immunofluorescence + histologic examination remains the diagnostic gold standard.