The aim of the present study was to determine whether routine integration of positron emission tomography (PET) with 18F-labeled fluorodeoxyglucose (FDG) in the planning of stereotactic brain biopsy increases the technique's diagnostic yield. Forty-three patients underwent combined FDG-PET- and computerized tomography (CT)-guided stereotactic biopsy of intracranial lesions according to a previously described technique. In 36 patients, an area of abnormal FDG uptake was used to guide at least one stereotactic biopsy trajectory. A total of 90 stereotactic trajectories were performed; among them, 55 were based on FDG-PET-defined targets and 35 were based on CT-defined targets. Histological diagnosis was obtained in all patients, but six of the 90 trajectories were nondiagnostic; all six were based on targets defined by CT only. Differences between the diagnostic yield of trajectories based on FDG-PET-defined targets and those based on CT-defined targets were statistically significant in patients with contrast-enhanced lesions, but not in patients with nonenhancing lesions. These results support the view the FDG-PET may contribute to the successful management of brain tumor patients requiring stereotactic biopsy. Because no significant increase in discomfort or morbidity related to the technique was found, it is suggested that the development of similar techniques integrating PET data in the planning of stereotactic biopsy should be considered by centers performing stereotactic surgery and having access to PET technology.