Single-isocenter, multitarget cranial stereotactic radiosurgery (SRS) is more efficient than using an isocenter for each target, but spatial positioning uncertainties can be magnified at locations away from the isocenter. This study reports on the spatial accuracy of two frameless, linac-based SRS systems for multitarget, single-isocenter SRS as a function of distance from the isocenter. One system uses the ExacTrac platform for image guidance and the other localizes with cone beam computed tomography (CBCT). For each platform, a phantom with 12 target BBs distributed up to 13.8 cm from the isocenter was aligned starting from five different initial offsets and then imaged with the treatment beam at seven different gantry and couch angles. The distribution of the resulting positioning errors demonstrated the value of adding a 1-mm PTV margin for targets up to about 7–8 cm from the isocenter. For distances 10 cm or more, the CBCT-based alignment remained within 1.1 mm while the ExacTrac-based alignment differed by up to 2.2 mm.