The Pelorus Mark III Stereotactic System is a commercially available device for CT-guided stereotactic brain biopsy in people. With relatively minor modifications, this device was used to safely and accurately perform CT-guided stereotactic brain biopsies in 50 dogs with intracranial lesions. Modifications were necessary to accommodate a 90 degree shift in orientation of the canine head compared to the human head during the imaging phase of the procedure, and to facilitate other phases of the biopsy procedure that are affected by the uneven and variable topography of the canine skull. Description of a typical CT-guided brain biopsy procedure in dogs using the modified Pelorus Mark III Stereotactic System is provided. Accuracy of biopsy needle placement was determined by comparing the x, y and z coordinates of the biopsy target site with the actual coordinates of the needle tip on CT images. Mean needle placement error was 3.5 +/- 1.6 mm. Needle placement error was not significantly related to operator experience, dog size (body weight), or needle path length, however, needle placement error was significantly affected by lesion location.