A canine case of Coombs' test positive and antinuclear antibody-negative hemolytic anemia was examined because of the development of skin lesions after 18 months treatment with prednisolone. Histopathological examination of biopsy specimens obtained from skin and oral mucosa revealed the acantholysis, edematous lesions of the stratum basale and mononuclear cell accumulation in the dermis. Deposits of immunoglobulin G and complement factor 3 were detected at the intercellular and dermoepidermal junction by the direct immunofluorescent test. From these results, the case was considered to be an autoimmune disease caused by distinct antibodies against different organs.