Intrathecal (IT) chemotherapy is an established method of preventing and treating CNS leukemia. Although this intervention is beneficial and necessary, understanding the potential adverse effects of IT chemotherapy is important so that these potential effects can be anticipated and prevented. Tumor lysis syndrome is a known complication of systemic chemotherapy and has also been reported as a rare complication after IT chemotherapy in patients with CNS disease. We report the first case of tumor lysis syndrome occurring in a patient with T-cell acute lymphoblastic leukemia without CNS disease. The systemic effects of the IT chemotherapy were confirmed by the decreased size of the presenting mediastinal mass.