Objective: To evaluate the diagnostic accuracy of the panoramic radiograph in judging the relationship between the impacted mandibular third molar (IMTM) and the inferior alveolar canal (IAC) by cone-beam computed tomography (CBCT) and give guidelines for using radiological examinations before IMTM extraction. Methods: A total of 1735 IMTMs on panoramic radiographs were analysed and classified into three classes according to the relationship between the IMTMs and the IAC. A total of 126 IMTMs superimposing on the canal partially or touching the canal in line on panoramic radiographs were examined by CBCT. Nine radiographic signs were observed by two radiologists respectively and multivariate logistic regression analysis was performed. Results: 8.7% of IMTMs have superimposition or a linear touching relationship with the IAC on panoramic radiographs. Of these IMTMs, 52.4% impinged and broke the IAC in CBCT images. Two radiologic signs on panoramic radiographs, including interruption of the radiopaque border of the canal (P = 0.009), and interruption of the alveolar lamina dura and periodontal space (P = 0.007), were statistically significant in predicting the impingement of the IAC. Conclusion: Panoramic radiography can be used to screen out high-risk cases of inferior alveolar nerve injury before the IMTM extraction. Those IMTMs superimposing the canal partially or touching the canal in line on panoramic radiographs should be examined by CBCT further. Two features on panoramic radiographs, including interruption of the alveolar lamina dura and periodontal space, and interruption of the radiopaque border of the canal, were more valuable than other signs to predict impingement and interruption of the IAC wall. Keywords: cone-beam computed tomography, impacted mandibular third molar, inferior alveolar canal, panoramic radiography