We report here a 16-year-old boy with pre-B-type acute lymphoblastic leukemia who developed acute tumor lysis syndrome (TLS) following 12 h mitoxantrone infusion. TLS is a distinct clinical entity which has been recognized most frequently with aggressive combination chemotherapy of rapidly proliferating hematologic neoplasms. There have been a few reports of single-agent-induced tumor lysis, but to our knowledge, this is the first case reported with mitoxantrone alone.