BACKGROUND Functional neuronavigation with intraoperative 3-dimensional (3D) ultrasound may facilitate safer brain lesion resections than conventional neuronavigation. OBJECTIVE In this study, functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTT) were used to map eloquent areas. We assessed the use of fMRI and DTT for preoperative assessments and determined whether using these data together with 3D ultrasound during surgery enabled safer lesion resection. METHODS We reviewed 51 consecutive patients with intracranial lesions in whom fMRI with or without DTT was used to map eloquent areas. To assess a possible impact of fMRI/DTT, we reviewed and analyzed the quality of the fMRI/DTT data, any change in therapeutic strategies, lesion to eloquent area distance (LEAD), extent of resection, and clinical outcome. RESULTS As a result of the fMRI/DTT mapping, the therapeutic strategies were changed in 4 patients. The median tumor residue for glioma patients was 11% (n = 33) and 0% for nonglioma lesions (n = 12). For gliomas, there was a significant correlation between decreasing LEAD and increasing tumor residue. Of the glioma patients, 42% underwent gross total resection (>or= 95%) and 12% suffered neurological worsening after surgery as a result of complications. Of glioma patients with an LEAD of <or= 5 mm, 24% underwent gross total resection and 10% experienced neurological deterioration. CONCLUSION This study demonstrates that preoperative fMRI and DTT had direct consequences for therapeutic strategies and indicates their impact on intraoperative strategies to spare eloquent cortex and tracts. Functional neuronavigation combined with intraoperative 3D ultrasound can, in most patients, enable resection of brain lesions with general anesthesia without jeopardizing neurological function.