BACKGROUND Cerebral thrombosis associated with protein S deficiency is very rare and is mainly related to hereditary form of protein S deficiency. CASE REPORT A 19-year-old girl with acute lymphoblastic leukemia presented hemianopsy within a few days after the first administration of L-asparaginase. Magnetic resonance of the brain showed a cortical infarct. A marked decrease of the level of protein S was documented. Few days later, the patient was free of symptoms and protein S level was restored to the normal suggesting that the cerebral thrombosis was caused by transient protein S deficiency induced by L-asparaginase administration. DISCUSSION Patients with neurological complication caused by L-asparaginase should be tested for protein S and other anticoagulant deficiencies.