One-and-a-half syndrome is a clinical disorder featuring extraocular movements characterized by horizontal conjugate gaze palsy with internuclear ophthalmoplegia. It usually results from a unilateral lesion of the midbrain, and the most common cause of this syndrome in young women is multiple sclerosis. We report the case of a 38-year-old woman diagnosed as having acute myeloblastic leukemia presenting with characteristic neurologic and imaging features of one-and-a-half syndrome. Hyperleukocytosis, cancer procoagulants, tissue factor expression, and the increased proteolysis of coagulation factors by leukemic cells may all contribute to the propensity for thrombotic vascular occlusion. The optimal treatment of acute brain infarction in acute leukemia patients with hyperleukocytosis remains unclear. However, this patient illustrates that leukapheresis alone can provide rapid and effective relief of visual symptoms without neurologic sequela. To achieve better outcomes and survival, clinicians must maintain a heightened awareness of this distinctly unusual manifestation.