A 20-year-old man with a history of pre-B cell acute lymphocytic leukemia (ALL) presented with optic perineuritis of the right eye while undergoing chemotherapy. Evaluation failed to reveal an infectious or neoplastic cause, and the patient improved with oral corticosteroid treatment. He returned 10 weeks later with complete loss of vision in the right eye. Optic nerve biopsy revealed leukemic infiltration of the optic nerve, and the patient was treated for central nervous system (CNS) relapse of ALL. Transient optic perineuritis may be the initial manifestation of CNS involvement of pre-B cell ALL.