Purpose: Preoperative radiographic assessment of the mandibular third molars is essential to prevent inferior alveolar nerve damage during extraction. The purpose of this study was to assess the reliability of panoramic signs of association between the roots of teeth and the canal, and to compare the panoramic signs with cone beam computed tomography (CBCT) findings. Materials and Methods: CBCT images of 132 impacted mandibular third molars were evaluated to determine the association of the root to the canal. The CBCT findings were compared with the corresponding panoramic images. Logistic regression analysis was used to define the diagnostic criteria of the panoramic images. Results: Among the panoramic signs, loss of the cortical line was the most frequent radiographic sign predicting association (sensitivity: 79.31). Contact of the tooth with the canal was observed in all cases in which the loss of cortical line of the canal or darkening of the roots was found on the panoramic radiographs. Conclusion: Darkening of the roots and loss of the cortical line on panoramic radiographs might be highly suggestive of the risk of nerve injury.