We report on dominantly inherited epidermal acantholysis in three dogs, a sire and two female offspring. The skin lesions were characterized by hairless, hypertrophic plaques. Histopathologically, these lesions showed epidermal hyperplasia with individual enlargement of keratinocytes, extensive acantholysis and minimal dyskeratosis. Ultrastructural analysis revealed that attachment plaques of desmosomes were still intact while some tonofilaments were detached from them in early lesions; there were well-developed microvilli at dissociated cell surfaces. The data imply that these animals have undergone a process similar to human benign familial chronic pemphigus (BFCP). Immunohistochemical examination revealed that staining for E-cadherin and actin variably remained in dissociated keratinocytes. Focal intracellular staining for desmosomal glycoproteins and desmosomal proteins were observed within the dissociated keratinocytes. This dominantly inherited acantholytic disease in dogs could be a useful animal model for investigating the pathogenesis of BFCP in humans.