This study is the first one to compare at baseline the clinical characteristics by means of the BPDAI score along with the concentrations of anti-BP180 and anti-BP230 antibodies in BP patients with and without mucosal involvement. Analysis of separate and independent BPDAI sub-scores highlighted that skin lesions, more specifically blisters, and erosions were more substantial in patients with mucosal involvement than in typical BP. Such clinical characteristics were associated with the absence of anti-BP230 autoantibody in the serum of BP patients with mucosal involvement. Furthermore, we showed that mucosal lesions are clinically mainly related to disease severity, but not only. Altogether, our results suggest that compared to the classical pathophysiological processes previously defined in BP (12, 16, 17, 24, 33–36), specific immunological mechanisms should be triggered to end with mucosal lesions.