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Ocular manifestations of leukemia are often bilateral and involve all ocular structures with non-specific features like retinal hemorrhages, cotton wool spots and choroidal infiltrates. We report a rare, atypical initial presentation of acute myeloid leukemia with unilateral central retinal vein occlusion in a middle-aged male. This case will raise awareness among ophthalmologists to recognize and diagnose underlying systemic disease early and decrease systemic morbidity in consultation with a hematologist.