A seven-year-old neutered male cocker spaniel was presented with an 11-month history of generalised bacterial dermatitis. There were skin lesions over the entire body, which were round, slightly raised and encrusted. Skin biopsies were collected and the histological findings were consistent with pemphigus foliaceus. Immunohistochemical staining by the indirect immunoperoxidase method was positive, with desmosomal deposition of immunoglobulin (Ig) G. Haematological analysis revealed a regenerative anaemia and profound thrombocytopenia, while a Coombs' test was positive for polyvalent canine Coombs' reagent and anti-dog IgG. An antinuclear antibody test was positive, with a titre of 10,240. An ophthalmic examination demonstrated low tear production (keratoconjunctivitis sicca). Seven months after initial referral, the dog was re-presented with severe generalised peripheral lymphadenopathy. Radiographic evaluation of the thorax and abdomen revealed enlarged cranial mediastinal and sublumbar lymph nodes. Tru-Cut biopsy from an enlarged lymph node confirmed the diagnosis of lymphoma, which was phenotyped as a B-cell tumour. The diagnosis in this case was systemic lupus erythematosus, with the unusual feature of pemphigus foliaceus, and subsequent development of B-cell lymphoma. The case adds further to knowledge of the protean clinical presentations of canine autoimmune diseases and provides additional evidence for the potential association between autoimmunity and immune-system neoplasia in this species.