"Duane," a 6-year-old castrated male Himalayan cat presented to the Dermatology Service at the Cornell University Hospital for Animals for evaluation of a progressively worsening, widespread crusting dermatopathy of approximately three months duration. On presentation, Duane had extensive areas of alopecia and crusting on his face, nasal planum, external pinnae, dorsum, and clawbeds. Thoracic radiographs ruled out the presence of a thymoma as a possible cause for the exfoliative dermatosis. Cytology of the crusting lesions revealed the presence of acantholytic keratinocytes and supported a diagnosis of pemphigus foliaceus. Histopathology of biopsies taken of affected skin verified the presence acantholytic keratinocytes and confirmed the diagnosis of pemphigus foliaceus. Immunosuppressive therapy using oral dexamethasone was started. Various adjustments to the treatment regimen were made as complications were encountered. This case illustrates the importance of accurately diagnosing pemphigus foliaceus and the challenges of effective treatment.