Background/Objectives: Periapical lesions (PLs) are frequently detected in dental radiology. Accurate diagnosis of these lesions is essential for proper treatment planning. Imaging techniques such as orthopantomogram (OPG) and cone-beam CT (CBCT) imaging are used to identify PLs. The aim of this study was to assess the diagnostic accuracy of artificial intelligence (AI) software Diagnocat for PL detection in OPG and CBCT images. Methods: The study included 49 patients, totaling 1223 teeth. Both OPG and CBCT images were analyzed by AI software and by three experienced clinicians. All the images were obtained in one patient cohort, and findings were compared to the consensus of human readers using CBCT. The AI’s diagnostic accuracy was compared to a reference method, calculating sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and F1 score. Results: The AI’s sensitivity for OPG images was 33.33% with an F1 score of 32.73%. For CBCT images, the AI’s sensitivity was 77.78% with an F1 score of 84.00%. The AI’s specificity was over 98% for both OPG and CBCT images. Conclusions: The AI demonstrated high sensitivity and high specificity in detecting PLs in CBCT images but lower sensitivity in OPG images.