Gemcitabine, a pyrimidine nucleoside analogue, is an oncologic agent used in the treatment of cutaneous T-cell lymphoma (CTCL). Common dermatologic reactions associated with gemcitabine include alopecia, mild skin rash, and mucositis but skin necrosis is exceptional. Herein we present an unusual case of widespread skin necrosis mimicking toxic epidermal necrolysis in a 45-year-old woman receiving gemcitabine therapy for stage IIIA cutaneous T-cell lymphoma. This is the first reported case of a TEN-like reaction subsequent to gemcitabine treatment. J Drugs Dermatol. 2018;17(5):582-585.