Bullous pemphigoid (BP) is an autoimmune blistering disease that targets the haemidesmosomal proteins, mainly BP180. Extracellular vesicles (EVs) have been demonstrated to carry tissue-specific autoantigens in the setting of autoimmune diseases and transplant organ rejection; this phenomenon was demonstrated to have pathogenic implications in autoimmune diseases and to correlate with transplant rejection severity. The purpose of this study was to identify the presence of BP targeted autoantigens in blister fluid derived EVs. We isolated, by size exclusion chromatography, EVs derived from blisters of BP-patients and from suction blisters of healthy donors. EV characterization was performed by flow cytometry and nanoparticle tracking analysis. Western blot analysis was used to investigate the presence of autoantigens. A suspension enriched in EVs was efficiently obtained from blister fluid from patients and healthy donors. EV-enriched fractions were enriched in particles with a size distribution characterizing small-EVs (main peak was present at 94.5 nm). BP180 was found, by western blot analysis, in EVs derived from blister fluid of 3 out 6 BP patients and in none of EVs isolated from suction blister fluid of healthy donors. BP230 and Dsg1 were not detectable in EVs of any of the samples. No specific clinical characteristics seemed to correlate to the presence of BP180 in EVs. The discovery of BP180 in EVs derived from blister fluid might help understanding BP pathogenesis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00403-023-02560-2.