The knowledge of root canal anatomy and of the anatomical relationship should be considered mandatory when planning surgical endodontics. The aim of the study was to investigate the anatomical features of mandibular premolars, evaluating their relationship with mental nerve. CBCT scans were evaluated recording the number of roots, root canal configuration and the relationship with mental nerve of 100 mandibular premolars. After simulating a resection of 3 mm of the root, the shape and the number of canals, and the distance to the buccal and lingual bone plate and to the mental foramen was evaluated. The one root - one canal configuration was the most common configuration. The mental foramen was located at the level of MSPs in 40% cases, and it was between MSP and MFP in 46% of cases. The distance between the apex and the vestibular plate was lower than the distance to the lingual one. We found a significant heterogeneity in the anatomy of mandibular premolars. CBCT could be considered important when planning surgical endodontics in this region.