OBJECTIVE The aim of this study was to compare the performance of cone-beam computerized tomography (CBCT) with multislice CT (MSCT) and single photon emission CT (SPECT) in the detection of bone invasion from oral malignancies. METHODS In this prospective investigation, 77 patients with histologically proven malignancy of the oral cavity received MSCT, CBCT, and SPECT imaging of the head presurgically. Radiologic evaluations were compared with histopathologic examinations of the resected tumor specimens. Receiver operating characteristic (ROC) analysis as well as the sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS The sensitivity, specificity, positive predictive value, and negative predictive value for MSCT were 0.8, 1.0, 1.0, and 0.75, respectively; for CBCT 0.92, 0.965, 0.98, and 0.875; and for SPECT 0.91, 0.4, 0.7, and 0.75. ROC analysis showed area under the curve values of 0.894 (95% confidence interval [CI] 0.806-0.982) for MSCT; 0.931 (95% CI 0.835-1.000) for CBCT, and 0.716 (95% CI 0.566-0.866) for SPECT. CONCLUSIONS CBCT is accurate in predicting malignancies' bone involvement and can compete with MSCT and SPECT in detecting bone invasion in patients with oral malignancies.