The positioning accuracy and precision of a head and neck immobilization device for radiation therapy of tumors in the canine skull was evaluated. Nineteen dogs with a spontaneous tumor of the head were enrolled including 12 with an intracranial mass and seven with an intranasal or maxillary tumor. Three hundred thirty-three pairs of orthogonal digital portal radiographs were analyzed to assess patient displacement in the cranial–caudal, lateral, and dorso-ventral directions. The mean systematic displacement was 0.8, 1, and 0.9 mm. The mean random displacement was 1.9, 1.6, and 1.5 mm. These values resulted in an overall displacement of 2.1 mm in the cranial–caudal direction, 1.8 mm in the lateral direction, and 1.7 mm in the dorsal–ventral direction. The mean displacement value of the three dimensional (3D) vector was 2.4 mm with a standard deviation of 2.1. Ninety-five percent of all vectors were <6.4 mm. This study quantifies the precision and accuracy of this particular positioning device. Knowing the limitations and setup variability of the system being used to set patients up for daily radiotherapy is paramount to planning and delivering appropriate radiation doses, especially as more complex treatment methods are used.