We describe here the first case of childhood acute promyelocytic leukemia (APL) with cutaneous infiltration of leukemic cells following treatment with all-trans retinoic acid (ATRA) confirmed by immunostaining and polymerase chain reaction for PML/RAR alpha. An 11-year-old girl was diagnosed as having APL. Chromosomal analysis demonstrated the characteristic karyotype of t(15;17). ATRA therapy was begun at a dose of 45 mg/m2 daily. During ATRA therapy, leukocytosis and retinoic acid syndrome were observed but were resolved by dexamethasone. Two months after commencement of ATRA therapy, complete remission was achieved. During the course of consolidation chemotherapy, however, multiple cutaneous nodules developed in her trunk, the size and number of which increased despite intensive chemotherapy. Histological and immunological studies of the cutaneous nodules showed infiltration of leukemic cells. PML/RAR alpha mRNA was detected in both the cutaneous nodules and bone marrow by means of polymerase chain reaction. ATRA treatment for APL may be associated with an increased incidence of extramedullary disease such as cutaneous lesions. The best available therapy for APL may be a combination of ATRA and chemotherapy, especially when a marked leukocytosis occurs during ATRA therapy.