Background: Some patients with pemphigus vulgaris (PV) have mucous membrane erosions with minimal skin involvement (mucosal dominant type), and others show extensive skin blisters and erosions in addition to mucous membrane involvement (mucocutaneous type). Patients with pemphigus foliaceus (PF) show only skin involvement. Objective: The purpose of this study is to determine whether there is a difference in autoantibody profile among mucosal dominant PV, mucocutaneous PV, and PF. Methods: Antibody titer against desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3) were measured with enzyme-linked immunosorbent assay using recombinant Dsg1 and Dsg3. Sera were obtained during clinically active disease from 24 patients with mucosal dominant PV, 20 with mucocutaneous PV, and 23 with PF. Results: All sera samples from patients with mucosal dominant PV sera were negative against Dsg1 but positive against Dsg3. All sera samples from those with mucocutaneous PV were positive against both Dsg1 and Dsg3. All sera samples from patients with PF were positive against Dsg1, but negative against Dsg3. Conclusion: Each subtype has its own anti-Dsg autoantibody profile, indicating that the clinical phenotype of pemphigus is defined by the autoantibody profile.