We report a 17-year-old boy with meningeal involvement of lymphoblastic lymphoma who experienced acute tumor lysis syndrome following intrathecal administration of methotrexate. Intrathecally injected methotrexate provides a slow- release reservoir of methotrexate into the bloodstream with prolonged cytotoxic levels. To the best of our knowledge, this is the second case of tumor lysis syndrome to be described after intrathecal methotrexate injection. The pathogenesis of this unusual complication of intrathecal chemotherapy is discussed.