Résumé : OBJECT: The aim of this study was to compare the contribution of the tracers 11C-methionine (Met) and 18F-fluorodeoxy-glucose (FDG) in positron emission tomography (PET)-guided stereotactic brain biopsy. METHODS: Forty-five patients underwent combined Met-PET and FDG-PET studies associated with computerized tomography (CT)- or magnetic resonance (MR)-guided stereotactic biopsy. Each patient presented with a lesion that was in proximity to the cortical or subcortical gray matter. The Met-PET and FDG-PET scans were analyzed to determine which tracer offers the best information to guide at least one stereotactic biopsy trajectory. Histologically based diagnoses were rendered in all patients (39 tumors, six nontumorous lesions) and biopsies were performed in all tumors with the aid of PET guidance. When tumor FDG uptake was higher than that in the gray matter (18 tumors), FDG was used for target definition. When FDG uptake was absent or equivalent to that in the gray matter (21 tumors), Met was used for target definition. Parallel review of all histological and imaging data showed that all tumors had an area of abnormal Met uptake and 33 had abnormal FDG uptake. All six nontumorous lesions had no Met uptake and biopsies were performed using CT or MR guidance only. All tumor trajectories had an area of abnormal Met uptake; all nondiagnostic trajectories in tumors had no abnormal Met uptake. CONCLUSIONS: When FDG shows limitations in target selection, Met is a good alternative because of its high specificity in tumors. Moreover, in the context of a single-tracer procedure and regardless of FDG uptake, Met is a better choice for PET guidance in neurosurgical procedures.