Local cutaneous reactions have been reported at injection sites of interferon therapy, but these are usually erythema or rarely induration. Skin necrosis at the injection site is rare. We describe here a patient with multiple sclerosis who presented with cutaneous necrosis at the injection sites of interferon-β. Biopsy of the necrotic lesion showed dermal vessel thrombosis and complete ischemic coagulative necrosis of epidermis and dermis.