The ability of Leksell GammaPlan to perform stereotactic space localizations with image sets where there is misalignment of the patient's head (stereotactic frame and fiducial apparatus) relative to the computed tomography (CT) scanner coordinate system was studied. Misalignment is sometimes necessary for patient comfort. Results equally apply to magnetic resonance imaging. Seven 0.5 mm diameter CT-visible spheres were rigidly mounted to a string tied tightly at each end to diagonally opposite posts attached to a Leksell stereotactic frame. A standard CT fiducial box was applied to the frame in the usual clinical manner. A baseline CT scan (1 mm slice thickness) was obtained with the fiducial box perfectly aligned with the scanner axis. After localization of the image set, the (x,y,z) coordinate of the center of each sphere was recorded. Repeat CT scans with varying fiducial box misalignments with the imaging axis were subsequently obtained. The mean difference between the base line and the respective coordinates in misaligned geometries was approximately 0.2 mm (sigma=0.2 mm), well within the accuracy of the image sets and the delivery of radiosurgery with the Gamma Knife.