Paget's disease is occasionally found as an incidental finding on bone scans performed for the evaluation of metastatic disease, which causes a diagnostic and a subsequent therapeutic dilemma. We have previously described the 'mouse Face' appearance of vertebrae on bone scans (increased uptake in the vertebral body, posterior elements, and the spinous process), which was fairly specific for Paget's disease in a small series. This retrospective study was undertaken to determine if this observation holds true in a larger series. Bone scans performed in 2,881 patients were randomly selected, and were reviewed by 2 physicians. Thirty-nine cases with a 'mouse Face' appearance were identified. Diagnosis was established in 30 of the 39 patients by correlative radiographic studies and/or clinical follow-up. Twenty patients were referred for the evaluation of possible metastases, and 7 were found to have metastases at the sites of 'mouse Face.' The other 13 had Paget's disease. However, 6 of the 7 patients with metastases had extravertebral findings compatible with multiple metastases, and the remaining patient had a 'mouse Face' lesion only, with a question of metastases. Ten patients were evaluated for Paget's disease or others, and none of them had metastases at the site of the 'mouse Face.' The 'mouse Face' appearance is more suggestive of Paget's disease than metastases even in patients with cancer. These patients should be assumed unlikely to have vertebral metestases, unless proven by another correlative radiologic study.