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A 4-year-old female German Spaniel was presented with anorexia. Clinically, the dog showed papular to ulcerative lesions on the nasal planum and on the tongue. Hematological, bacteriological and mycological examinations did not contribute any evidence for the etiology of the lesions. Histopathological examination of skin biopsies revealed a proliferative dermatitis and folliculitis with hydropic degeneration of keratinocytes and cytoplasmatic inclusion bodies. Cowpox virus antigen was detected by immunohistochemistry, and electron microscopy showed pox virus particles in the cytoplasm of the epithelial cells. DNA of Orthopoxvirus bovis was identified by polymerase chain reaction. Consequently, in dogs with papular to ulcerative lesions in the face or on the tongue, infection with cowpoxvirus should be considered as an etiological differential diagnosis. Infected dogs represent a potential risk of infection for humans and other animals with close contact.