BACKGROUND/AIM: Unilateral choroidal infiltration as the initial manifestation of leukemic relapse in adults is rare, particularly after an extended period of remission. This report describes this unique ophthalmic presentation, highlights the associated diagnostic challenges, and reviews the literature. METHODS: Two cases are described and an extensive literature review was conducted. RESULTS: A 59-year-old male with acute lymphoid leukemia, in remission for 18 months, presented with unilateral scleritis, exudative retinal detachment, and choroidal thickening. A 57-year-old male with a history of acute myeloid leukemia, in remission for 4 years, presented with unilateral choroidal thickening leading to secondary angle closure. In both cases, there was a significant lag from the onset of eye symptoms to establishing a systemic diagnosis of acute leukemia, leading to a delay in definitive systemic treatment, despite a high suspicion of disease based on ophthalmic findings. CONCLUSIONS: These two cases illustrate the fundus findings consistent with leukemic choroidal infiltration that can represent the first sign of relapsed leukemia. The successful treatment of these patients hinges on collaboration between ophthalmologists and oncologists to optimize patient outcomes, highlighting the need for both groups to be aware of this rare ophthalmic presentation.