This study compared digital and digitized panoramic radiographs to detect incipient periapical lesions using the digital subtraction radiography (DSR) technique. Bone defects were created in 77 apical sites of dried human mandibles through the application of 70% perchloric acid. Conventional and digital radiographs were obtained twice at time zero and 2, 4, and 6 hours after application of the acid solution. Conventional radiographs were digitized by using the same attributes than direct digital radiographs. The baseline images were subtracted of the negative control and experimental groups and assessed by an experienced and blinded observer who assigned score 0 (normal) or 1 (mineral loss) to each image. The sensitivity of both modalities was statistically different in relation to experimental times. The percentage of correct responses significantly increased regarding experimental times. The specificity was high both for digitized and digital images. DSR of panoramic images, both digitized and digital, allows for the diagnosis of incipient-simulated periapical lesions with no differences in their performance.