Diffuse infiltrative lymphocytosis syndrome (DILS) is a hyperimmune reaction against HIV. It leads to MHC-restricted clonal expansion of CD8 T cells characterized by circulating CD8 hyperlymphocytosis and CD8 T-cell infiltration in organs. Our patient presented with painful lumbosacral radiculoplexus neuropathy and tested positive for HIV. Nerve biopsy showed large collections of CD8 lymphocytes suspicious for lymphoma. Symptoms, signs, and repeat biopsy improved with antiretroviral treatment. The presentation and treatment response suggest that this case is localized DILS.