Primary intraocular lymphoma is almost always a central nervous system B-cell non-Hodgkin lymphoma. Primary intraocular lymphoma is commonly diagnosed by demonstrating lymphoma cells in the vitreous or cerebrospinal fluid. An interleukin (IL) 10 to IL-6 ratio greater than 1.0 in these fluids and the detection of immunoglobulin gene rearrangement are useful adjuncts in the diagnosis of primary intraocular lymphoma. We report a case of primary intraocular lymphoma diagnosed by chorioretinal biopsy in which no malignant cells were identified in the vitreous and in which the IL-10 to IL-6 ratio was less than 1.0. The detection of IgH gene rearrangement heterogeneity in the tumor cells by polymerase chain reaction, a high tumor mitotic figure rate, and the rapid onset of multiple brain lesions suggest an aggressive malignant neoplasm.