We report a 13-year-old boy with Lennox-Gastaut syndrome (LGS) associated with leukoencephalopathy, He was diagnosed with unclassified acute lymphocytic leukemia at the age of 3 years. After initial chemotherapy, he received intravenous methotrexate (total dosage 1,035 mg), intrathecal methotrexate (total dosage 221 mg), and whole brain irradiation (2,400 cGy), From about the age of 8 years, he developed slurred speech, hyperactivity, and mental deterioration, Cranial CT revealed calcification of the subcortical white matter, At age 9 years, he exhibited tonic seizures and atonic seizures, EEG showed diffuse slow spike-wave discharges, which are characteristic of LGS, Although multiple antiepileptic drugs have been prescribed, the frequency of seizures remains unchanged and his mental state is becoming progressively worse.