Background: Patients with intraocular involvement by Hodgkin's disease may present with a variety of ocular abnormalities. Intraocular infections also have been reported in these patients, including two cases of cytomegalovirus retinitis (CMV) diagnosed on postmortem examination. It often is difficult to differentiate between these conditions on clinical examination. Methods: A patient with Hodgkin's disease presented with an atypical retinitis, vasculitis, and a serous macular detachment, Results of clinical examination, fluorescein angiography, and vitreous biopsy for culture and polymerase chain reaction (PCR) testing are described. Results: The diagnosis of an atypical CMV retinitis simulating possible intraocular involvement by Hodgkin's disease was confirmed by PCR testing of undiluted vitreous, Intravenous therapy with foscarnet, guided by the results of the vitreous biopsy, resulted in resolution of the retinitis and an improvement in vision. Conclusion: Intraocular involvement by cytomegalovirus retinitis can simulate intraocular lymphoma in a patient with Hodgkin's disease. Polymerase chain reaction testing was useful in establishing the diagnosis and guiding successful therapy in this patient.