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Background Deep learning (DL) may facilitate the diagnosis of various pancreatic lesions at imaging. Purpose To develop and validate a DL-based approach for automatic identification of patients with various solid and cystic pancreatic neoplasms at abdominal CT and compare its diagnostic performance with that of radiologists. Materials and Methods In this retrospective study, a three-dimensional nnU-Net-based DL model was trained using the CT data of patients who underwent resection for pancreatic lesions between January 2014 and March 2015 and a subset of patients without pancreatic abnormality who underwent CT in 2014. Performance of the DL-based approach to identify patients with pancreatic lesions was evaluated in a temporally independent cohort (test set 1) and a temporally and spatially independent cohort (test set 2) and was compared with that of two board-certified radiologists. Performance was assessed using receiver operating characteristic analysis. Results The study included 852 patients in the training set (median age, 60 years [range, 19-85 years]; 462 men), 603 patients in test set 1 (median age, 58 years [range, 18-82 years]; 376 men), and 589 patients in test set 2 (median age, 63 years [range, 18-99 years]; 343 men). In test set 1, the DL-based approach had an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.89, 0.94) and showed slightly worse performance in test set 2 (AUC, 0.87 [95% CI: 0.84, 0.89]). The DL-based approach showed high sensitivity in identifying patients with solid lesions of any size (98%-100%) or cystic lesions measuring 1.0 cm or larger (92%-93%), which was comparable with the radiologists (95%-100% for solid lesions [P = .51 to P > .99]; 93%-98% for cystic lesions ≥1.0 cm [P = .38 to P > .99]). Conclusion The deep learning-based approach demonstrated high performance in identifying patients with various solid and cystic pancreatic lesions at CT. © RSNA, 2022 Online supplemental material is available for this article.