Case summary A 6-year-old neutered female European Shorthair cat was referred for chronic, moderately pruritic, alopecic and exfoliative dermatosis that was unresponsive to antiparasitic, antibiotic or steroidal anti-inflammatory drugs. The cat presented with truncular alopecia and numerous whitish adherent scales covering the whole body. Differential diagnoses included sebaceous adenitis, dermatophytosis, demodicosis, exfoliative dermatitis associated or not with thymoma, drug reaction, feline immunodeficiency virus- or feline leukaemia virus-associated dermatoses, epitheliotropic T-cell lymphoma, and Malassezia yeasts and/or bacterial overgrowth. Blood tests were within normal limits and the retrovirus tests were negative. Skin scrapings, fungal culture, coat brushing and skin cytology were negative for parasitic or microbial elements. Radiographs showed no signs of a thymic mass. Histological examination of skin biopsies revealed marked orthokeratotic hyperkeratosis, lymphocytic (CD3+) interface dermatitis and mural folliculitis with absence of sebaceous glands and occasional apoptotic cells in different epidermal layers. Clinical and histological findings were consistent with non-thymoma-associated exfoliative dermatitis syndrome. Ciclosporin A (7 mg/kg) was administered once daily. A dramatic improvement was observed after 3 weeks. Ciclosporin A intake was then progressively spaced out as the clinical signs diminished. Skin biopsies revealed resolution of hyperkeratosis, disappearance of the inflammatory infiltrate and recovery of the sebaceous glands. Relevance and novel information T-cell infiltration with signs of epidermal cytotoxicity, in the absence of infectious agents or neoplastic process, suggests an immune-mediated process, and ciclosporin A, a calcineurin inhibitor, would be the drug of choice. This is the first report showing resolution of both the clinical and histological signs of non-thymoma-associated exfoliative dermatitis.