BACKGROUND: Precise robotic or stereotactic implantation of stereoelectroencephalography (sEEG) electrodes relies on the exact referencing of the planning images in order to match the patient's anatomy to the stereotactic device or robot. We compared the accuracy of sEEG electrode implantation with stereotactic frame versus laser scanning of the face based on computed tomography (CT) or magnetic resonance imaging (MRI) datasets for referencing. METHODS: The accuracy was determined by calculating the Euclidian distance between the planned trajectory and the postoperative position of the sEEG electrode, defining the entry point error (EPE) and the target point error (TPE). The sEEG electrodes (n = 171) were implanted with the robotic surgery assistant (ROSA) in 19 patients. Preoperative trajectory planning was performed on three-dimensional (3D) MRI datasets. Referencing was accomplished either by performing (A) 1.25-mm slice CT with the patient's head fixed in a Leksell stereotactic frame (CT-frame, n = 49), fused with a 3D-T1-weighted, contrast enhanced- and T2-weighted 1.5 Tesla (T) MRI; (B) 1.25 mm CT (CT-laser, n = 60), fused with 3D-3.0-T MRI; (C) 3.0-T MRI T1-based laser scan (3.0-T MRI-laser, n = 56) or (D) in one single patient, because of a pacemaker, 3D-1.5-T MRI T1-based laser scan (1.5-T MRI-laser, n = 6). RESULTS: In (A) CT-frame referencing, the mean EPE amounted to 0.86 mm and the mean TPE amounted to 2.28 mm (n = 49). In (B) CT-laser referencing, the EPE amounted to 1.85 mm and the TPE to 2.41 mm (n = 60). In (C) 3.0-T MRI-laser referencing, the mean EPE amounted to 3.02 mm and the mean TPE to 3.51 mm (n = 56). In (D) 1.5-T MRI, surprisingly the mean EPE amounted only to 0.97 mm and the TPE to 1.71 mm (n = 6). In 3 cases using CT-laser and 1 case using 3.0 T MRI-laser for referencing, small asymptomatic intracerebral hemorrhages were detected. No further complications were observed. CONCLUSION: Robot-guided sEEG electrode implantation using CT-frame referencing and CT-laser-based referencing is most accurate and can serve for high precision placement of electrodes. In contrast, 3.0-T MRI-laser-based referencing is less accurate, but saves radiation. Most trajectories can be reached if alternative routes over less vascularized brain areas are used. This article is part of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and Beyond".