Introduction The Gamma Knife® planning software (TMR 10, Elekta Instruments, AB, Sweden) affords two ways of defining the skull volume, the “historical” one using manual measurements (still perform in some centers) and the new one using image-based skull contours. Our objective was to assess the potential variation of the dose delivery calculation using consecutively in the same patients the two above-mentioned techniques. Materials and methods We included in this self-case-control study, 50 patients, treated with GKRS between July 2016 and January 2017 in Lausanne University Hospital, Switzerland, distributed among four groups: convexity targets (n = 18), deep-seated targets (n = 13), vestibular schwannomas (n = 11), and trigeminal neuralgias (n = 8). Each planning was performed consecutively with the 2 skull definition techniques. For each treatment, we recorded the beam-on time (min), target volume coverage (%), prescription isodose volume (cm3), and maximal dose (Gy) to the nearest organ at risk if relevant, according to each of the 2 skull definition techniques. The image-based contours were performed using CT scan segmentation, based upon a standardized windowing for all patients. Results The median difference in beam-on time between manual measures and image-based contouring was + 0.45 min (IQR; 0.2–0.6) and was statistically significant (p < 0.0001), corresponding to an increase of 1.28% beam-on time per treatment, when using image-based contouring. The target location was not associated with beam-on time variation (p = 0.15). Regarding target volume coverage (p = 0.13), prescription isodose volume (p = 0.2), and maximal dose to organs at risk (p = 0.85), no statistical difference was reported between the two skull contour definition techniques. Conclusion The beam-on time significantly increased using image-based contouring, resulting in an increase of the total dose delivery per treatment with the new TMR 10 algorithm. Other dosimetric parameters did not differ significantly. This raises the question of other potential impacts. One is potential dose modulation that should be performed as an adjustment to new techniques developments. The second is how this changes the biologically equivalent dose per case, as related to an increased beam on time, delivered dose, etc., and how this potentially changes the radiobiological effects of GKRS in an individual patient.