Chemotherapy-induced acral erythema is an uncommon and dramatic reaction to high-dose chemotherapy. It is characterized by painful erythema of both palms and soles with symmetrically well-defined borders, which may progress to bullae formation and desquamation. The bullous variant of this reaction has been reported with methotrexate and more frequently cytosine arabinoside. Rapid differential diagnosis and discrimination from more serious conditions such as graft versus host disease or toxic epidermal necrolysis is essential. In this case report, we present a 13-year-old boy who developed severe and prolonged chemotherapy-induced acral erythema after high-dose methotrexate treatment and successfully responded to intravenous immunoglobulin.