A 45-year-old man was diagnosed with diffuse large B-cell lymphoma stage IV which was confirmed by celiac lymph node biopsy. He subsequently completed six cycles of R-CHOP chemotherapy. Six months later, he presented with panuveitis OU with positive relative afferent pupillary defect OD. OCT revealed hyper-reflective lesions and irregularity of the retinal pigment epithelium OU. Fundus fluorescein angiogram shows hyper-auto fluorescence and granular changes on the retina. A month later, he developed swollen optic disc OD and hemorrhagic retinitis OU and treated as presumed CMV retinitis. Anti-TB was started after a positive Mantoux test. He finally consented for a vitreous biopsy which showed atypical lymphoid cells highly suggestive for vitreoretinal lymphoma and subsequently received intravitreal methotrexate OU.CONCLUSION: Optic nerve infiltration in systemic metastatic retinal lymphoma may have initial occult signs but with profound visual loss. Ocular infections like CMV retinitis and tuberculosis may mask and delay the diagnosis in immunocompromised patients.