Chemotherapy-induced acral erythema (CIAE) is a toxic reaction to a number of different chemotherapeutic agents, and causes symmetrical, well-demarcated, painful erythema on the palms and soles which is self-limiting. CIAE with bullous reaction in relation to methotrexate has been reported, but it is more commonly associated with cytosine arabinoside. The differential diagnosis of this condition from more serious conditions such as graft-vs-host disease or toxic epidermal necrolysis is essential.