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The aims of this study were to determine whether lesion features appear differently on panoramic radiography (PAN) and cone beam computed tomography (CBCT), and whether the use of CBCT affects diagnostic accuracy and observers' confidence in comparison with PAN.Three oral and maxillofacial radiologists reviewed 33 sets of PAN images and CBCT volumes of biopsy-proven lesions. They described 12 different lesion features and provided up to 3 ranked differential diagnoses, as well as their confidence with respect to those diagnoses. Their confidence was weighted by the rank at which the correct diagnosis was provided.Odds ratios (ORs) were statistically significant for border definition (OR = 5.45; P = .004), continuity of border cortication (OR = 0.34; P = .035), effect on neurovascular canals (OR = 6.38; P = .043), expansion (OR = 18.56; P < .001), cortical thinning (OR = 30.22; P < .001), and cortical destruction (OR = 9.80; P < .001). There was no association between the 2 modalities and the rank at which the correct differential diagnoses were made or the observers' weighted confidence.Before acquiring a CBCT scan to aid in the diagnosis of an intraosseous lesion, clinicians should consider the diagnostic information that is expected to be gained. In this study, although there were differences between PAN and CBCT with respect to some lesion features, CBCT did not help improve diagnostic accuracy.