We report a challenging case of HIV-associated neurocognitive disorder with superimposed Epstein-Barr virus (EBV) encephalitis. The patient presented with an abnormal MRI brain scan, and EBV DNA that was detected in the cerebrospinal luid and brain biopsy, which also demonstrated histopathological indings consistent with the diagnosis. This occurred on the background of a 12-month period of gradual cognitive decrease secondary to HIV-associated dementia. Invasive testing was required to reach the diagnosis in this case, highlighting the importance of thorough investigation of neurological impairment in HIV-positive patients. Clinicopathological recovery was achieved through optimization of antiretroviral therapy and use of valganciclovir.