OBJECT: Surface-based registration (SBR) with facial surface scans has been proposed as an alternative for the commonly used fiducial-based registration in image-guided neurosurgery. Recent studies comparing the accuracy of SBR and fiducial-based registration have been based on a few targets located on the head surface rather than inside the brain and have yielded contradictory conclusions. Moreover, no visual feedback is provided with either method to inform the surgeon about the estimated target registration error (TRE) at various target locations. The goals in the present study were: 1) to quantify the SBR error in a clinical setup, 2) to estimate the targeting error for many target locations inside the brain, and 3) to create a map of the estimated TRE values superimposed on a patient's head image. METHODS: The authors randomly selected 12 patients (8 supine and 4 in a lateral position) who underwent neurosurgery with a commercial navigation system. Intraoperatively, scans of the patients' faces were acquired using a fast 3D surface scanner and aligned with their preoperative MR or CT head image. In the laboratory, the SBR accuracy was measured on the facial zone and estimated at various intracranial target locations. Contours related to different TREs were superimposed on the patient's head image and informed the surgeon about the expected anisotropic error distribution. RESULTS: The mean surface registration error in the face zone was 0.9 +/- 0.35 mm. The mean estimated TREs for targets located 60, 105, and 150 mm from the facial surface were 2.0, 3.2, and 4.5 mm, respectively. There was no difference in the estimated TRE between the lateral and supine positions. The entire registration procedure, including positioning of the scanner, surface data acquisition, and the registration computation usually required < 5 minutes. CONCLUSIONS: Surface-based registration accuracy is better in the face and frontal zones, and error increases as the target location lies further from the face. Visualization of the anisotropic TRE distribution may help the surgeon to make clinical decisions. The observed and estimated accuracies and the intraoperative registration time show that SBR using the fast surface scanner is practical and feasible in a clinical setup.