Purpose: To report a case of systemic diffuse large B cell lymphoma presenting with ocular manifestations and neurologic findings resembling Vogt-Koyanagi-Harada syndrome. Observations: A 51-year-old Caucasian man presented with headache, ear pain, and blurry vision in both eyes. He was found to have bilateral exudative retinal detachments. After a short period of initial improvement with high dose systemic corticosteroid, his condition significantly worsened. An extensive work-up, including a kidney biopsy, led to a diagnosis of systemic diffuse large B cell lymphoma. He had excellent recovery following treatment with appropriate chemotherapy. Conclusions and Importance: Systemic malignancy may present with ocular manifestations and may masquerade as another diagnosis. An unexpected clinical course may suggest an alternative diagnosis. A broad systemic work-up including an evaluation for malignancy should be considered for patients presenting with unexplained exam or systemic findings.