The study aim was to develop and assess the performance of a deep learning (DL) algorithm in the detection of radiolucent intraosseous jaw lesions in cone beam computed tomography (CBCT) volumes. A total of 290 CBCT volumes from more than 12 different scanners were acquired. Fields of view ranged from 6 × 6 × 6 cm to 18 × 18 × 16 cm. CBCT volumes contained either zero or at least one biopsy-confirmed intraosseous lesion. 80 volumes with no intraosseous lesions were included as controls and were not annotated. 210 volumes with intraosseous lesions were manually annotated using ITK-Snap 3.8.0. 150 volumes (10 control, 140 positive) were presented to the DL software for training. Validation was performed using 60 volumes (30 control, 30 positive). Testing was performed using the remaining 80 volumes (40 control, 40 positive). The DL algorithm obtained an adjusted sensitivity by case, specificity by case, positive predictive value by case, and negative predictive value by case of 0.975, 0.825, 0.848, and 0.971, respectively. A DL algorithm showed moderate success at lesion detection in their correct locations, as well as recognition of lesion shape and extent. This study demonstrated the potential of DL methods for intraosseous lesion detection in CBCT volumes.