OBJECTIVE: To review the clinical utility of endoretinal biopsies in diagnostically undefined cases of vitreoretinal lymphoma (VRL) with negative vitreous cytology. METHODS: Retrospective case series including all consecutive patients who underwent endoretinal biopsies in a tertiary care center, Hospital Clinic of Barcelona (Spain), between 2014 and 2020. RESULTS: A total of 5 patients were included in this study. Four were male and one was female, with a mean age at diagnosis of 49years. Two patients had a past medical history of extraocular involvement, both having experienced complete remission of diffuse large B-cell lymphomas (DLBCL). All patients presented retinitis-like lesions characterized by substantial retinal thickening and infiltrative deposits below the retinal pigment epithelium (RPE). Retinal biopsies clarifying the diagnosis of VRL were established in four out of the five patients. Immunohistochemical results confirmed DLBCL, enabling the diagnosis of intraocular secondary DLBCL in two patients and primary ocular DLBCL in the other two. No postoperative complications were reported. CONCLUSIONS: Endoretinal biopsies clarified the diagnosis of vitreoretinal lymphoma (VRL) in 4 of 5 patients. This is a high rate of diagnosis, which is clinically meaningful, since it influences management. Our case series underscores the efficacy of employing retinal biopsy in cases where vitreous biopsy results prove inconclusive within the challenging context of suspicion of VRL.