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Lymphomatoid granulomatosis, a rare condition in children, affects the lungs primarily but may have significant extrapulmonary manifestations, especially in the central nervous system. We report a case of lymphomatoid granulomatosis with onset after the completion of chemotherapy for childhood acute lymphoblastic leukemia. Two months after treatment ended, the 7-year-old girl developed splenomegaly, cervical adenopathy, and bilateral interstitial pulmonary infiltrates. She improved on cefotaxime but experienced a seizure 1 month later. A computed tomography scan of the head was normal, but her pulmonary infiltrates had become nodular. A computed tomography-guided biopsy of 1 of the nodules revealed cellular interstitial pneumonitis. One month later, she had persistent pulmonary infiltrates, marked splenomegaly, and new seizures. Magnetic resonance imaging of the head revealed cerebral nodules. Itraconazole was begun, and the pulmonary infiltrates resolved. Five months after her initial symptoms, she developed tonic pupil and a decreased level of consciousness. Dexamethasone was initiated. Needle biopsies of the brain were carried out, yielding the diagnosis of severe chronic inflammatory changes focally consistent with granuloma. The child redeveloped splenomegaly and fever, and then suffered an acute decompensation with hypoxemia, tachypnea, splenomegaly, and cardiac gallop. Open-lung biopsy revealed lymphomatoid granulomatosis. Lymphoma-directed therapy was initiated, and the patient had complete resolution of pulmonary and cerebral nodules 5 months later. No intrathecal chemotherapy was administered, and radiation therapy was not necessary. Neuropsychological testing obtained after completion of therapy revealed an improvement in attention, coordination, and fine motor speed over time. She is now in good health and attending school.