BackgroundErythema multiforme (EM) is an uncommon cutaneous reaction pattern characterised by panepidermal keratinocyte apoptosis with lymphocytic satellitosis, and is reported in domestic animal species, livestock and rarely ferrets.Hypothesis/ObjectivesThe aim of this study was to analyse the spectrum of cutaneous clinical and histological features in ferrets with EM and to evaluate history and treatment outcomes.AnimalsFive client‐owned ferrets with biopsy‐confirmed EM.Materials and MethodsRetrospective review of electronic medical records and histopathological reports from 2002 to 2021. Tissue blocks, haematoxylin and eosin re‐cuts, and unstained slides were collected to review EM lesions and evaluate for infectious agents with special stains. Immunohistochemical staining was performed to assess cases for viral pathogens.ResultsPanepidermal cytotoxic dermatitis consistent with EM was identified in all cases and involved haired skin in four of five and mucous membranes in one of five ferrets. Skin lesions included variably pruritic alopecia, erythema, scaling, crusts and erosions/ulcerations. Histological features included primarily parakeratotic hyperkeratosis, panepidermal keratinocyte apoptosis, lymphocytic satellitosis and interface dermatitis. Superficial colonisation by bacteria, yeasts or by both was a common finding. Four of five ferrets had concurrent adrenal disease, one of which had resolution of skin lesions with deslorelin acetate treatment.Conclusions and Clinical RelevanceAwareness of the distinct clinical and histological features is key to the diagnosis of EM in ferrets. Clinical resolution was observed with gonadotropin‐releasing hormone agonists in two cases, suggesting that adrenal disease should be ruled out as a potential trigger of EM in ferrets.