Chemotherapy-induced acral erythema is an uncommon and distinctive syndrome of intense macular erythema of the palms and fingers seen in patients treated with high-dose chemotherapy. It is painful, may form bullae, and heals uneventfully with desquamation. The incidence (35%) of this complication in patients receiving bone marrow transplantation at our institution is quite high and probably reflects the exceptional doses of chemotherapy and concomitant total body irradiation these patients receive. Biopsy specimens showed vacuolar change, spongiosis, necrotic keratinocytes, and epidermal atypia. These findings probably result from direct toxic effect and mimic those of acute graft-vs-host disease. Awareness of chemotherapy-induced acral erythema is important to avoid its misdiagnosis as a cutaneous sign of acute graft-vs-host disease. This distinction can usually be made on clinical grounds. If necessary, serial skin biopsy specimens are helpful.