The aim of this study was to evaluate the ability to identify the contiguity between the root of the mandibular third molar and the mandibular canal (MC) in panoramic radiographs compared with Cone Beam-CT. Panoramic radiographs of 326 third molars and CBCT radiographs of 86 cases indicated for surgery and considered at risk were evaluated. The following signs were assessed in panoramic radiographs as risk factors: radiolucent band, loss of MC border, change in MC direction, MC narrowing, root narrowing, root deviation, bifid apex, superimposition, and contact between the root third molar and the MC. Radiographic signs associated with absence of MC cortical bone are: radiolucent band, loss of MC border, change in MC direction, and superimposition. The number of risk factors was significantly increased with an increasing depth of inclusion. CBCT revealed a significant association between the absence of MC cortical bone and a lingual or interradicular position of the MC. In cases in which panoramic radiographs do not exclude contiguity between the MC and tooth, careful assessment the signs and risks on CBCT radiographs is indicated for proper identification of the relationships between anatomic structures.