An infant with acute monoblastic leukemia who presented with an extramedullary mass and involvement of the bone marrow, cerebrospinal fluid, and skin is described. After achieving remission, she later developed a relapse that was isolated in the skin. Superficial electron beam irradiation to the total skin surface was administered as therapy for the relapse. She remains in remission 12 months following this treatment. The isolated nature of the skin relapse, in addition to the fact that the relapse did not involve a previously irradiated field, suggests that the skin may have harbored the leukemic cells since the time of diagnosis. Cytogenetic data is presented that lends further support to this hypothesis.