To report a patient with vitreoretinal lymphoma (VRL) secondary to systemic diffuse large B-cell lymphoma, who had two episodes of spontaneous regression.

An 80-year-old Nicaraguan male with a history of treated systemic diffuse large B-cell lymphoma presented with decreased vision in his right eye over one year. The patient was found to have subretinal lesions and moderate vitreous opacities in his right eye. Cytological analysis of vitreous confirmed B-cell lymphoma. Following his systemic work-up, spontaneous clinical improvement was noted. There were no vitreoretinal or systemic lymphoma recurrences during one year of follow-up until the patient had new onset decreased vision in the left eye. He was presumed to have a recurrence of VRL supported by optical coherence tomography findings. Repeat systemic workup was negative for reoccurrence and the ocular lesions resolved spontaneously over 4 weeks.

Spontaneous regression of intraocular lymphoma can rarely occur. Multimodal imaging has an essential role in diagnosing and monitoring recurrence of this disease.