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To analyze vitreoretinal findings, immunoglobulin clonality tests, and interleukin (IL) levels for diagnosing vitreoretinal lymphoma (VRL).Forty-three patients who underwent diagnostic vitrectomy for suspected VRL were retrospectively reviewed. Of those patients finally diagnosed with VRL and nonlymphoma, ophthalmic evaluation and cytology results, IL-6 and IL-10 levels, and immunoglobulin heavy chain and immunoglobulin kappa light chain clonality assays were compared.Sub-retinal pigment epithelium infiltration and veil-pattern vitreous opacity were specific vitreoretinal findings in patients with VRL. The area under the receiver operating characteristic curve of the IL-10-to-IL-6 ratio and of IL-10 levels was 0.972 and 0.931, respectively. A combined immunoglobulin heavy chain and immunoglobulin kappa light chain assay showed increased sensitivity, whereas the determined specificity of immunoglobulin kappa light chain, at 94.12%, was much higher than the 78.95% of immunoglobulin heavy chain. Patients with VRL with atypically elevated IL-6 levels showed extensive and severe sub-retinal pigment epithelium infiltration.Newly screened immunoglobulin kappa light chain clonality assays may be useful to distinguish VRL from uveitis with high specificity. When sub-retinal pigment epithelium or retinal infiltration is severe and extensive, the IL-10-to-IL-6 ratio may not be typical and should be carefully interpreted.