Enfortumab vedotin is an antibody-drug conjugate targeting nectin-4 and is being studied in the treatment of various epithelial carcinomas including urothelial carcinoma; early data suggests efficacy and tolerability. Rash has been described as an adverse event associated with treatment with enfortumab vedotin, but has not been characterized to date. We report a patient with metastatic urothelial carcinoma treated with enfortumab vedotin who developed erythematous, scaly papules and plaques on his torso and extremities with corresponding histologic features of vacuolar interface dermatitis and maturation disarray of keratinocytes. He was successfully treated with topical corticosteroids. Cutaneous toxicity appears to be a common adverse reaction in this growing class of antibody-drug conjugates.