OBJECTIVE To evaluate the utility of ¹⁸F-FDG PET/CT in suspected cerebral pathology in HIV-infected individuals. METHODS ¹⁸F-FDG PET/CT scans from 29 HIV-infected individuals (29 brain scans, 22 whole-body scans) who presented with neurological symptoms and signs were retrospectively reviewed and compared with subsequent clinical investigations. RESULTS The majority of patients (n=25) were referred to differentiate infection from malignant causes of cerebral pathology. Ten of the 11 patients with an eventual diagnosis of toxoplasmosis infection were correctly diagnosed by ¹⁸F-FDG PET/CT showing lesional uptake less than that of normal brain cortex (mean SUVmax 3.5, range 1.9 - 5.8). All five patients with a final diagnosis of primary central nervous system lymphoma (PCNSL) were correctly diagnosed by ¹⁸F-FDG PET/CT showing lesional uptake greater than that of normal brain cortex (mean SUVmax 18.8, range 12.4 - 29.9). Four of the five patients with ¹⁸F-FDG PET/CT features suggesting a vasculitic process had vasculitis confirmed as the final diagnosis. Three patients showed variable uptake in multiple cerebral lesions (including final diagnoses of tuberculosis and metastases from lung cancer in two patients) and there were four other miscellaneous diagnoses. In 12 patients biopsies were performed at sites guided by PET abnormality (7 brain, 5 lymph nodes) confirming or excluding significant disease in 11. CONCLUSIONS ¹⁸F-FDG PET/CT is particularly useful for differentiating between infection and PCNSL in HIV-infected patients with a cerebral lesion on MRI or CT. ¹⁸F-FDG PET/CT was also a helpful tool in the diagnostic work-up of patients with other HIV-related cerebral pathology. Additional advantages of ¹⁸F-FDG PET/CT are the abilities to assess abnormally increased glucose metabolism in the body and to identify potential sites for biopsy.