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The aim of this study was to evaluate the diagnostic criteria of dual time point Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in differentiating malignant from benign focal hypermetabolic lesions of duodenum.A total of 50 patients underwent 18F-FDG PET/CT at 2 points: 60 ± 13.7 minutes (early imaging) and 120 ± 26.4 minutes (delayed imaging) after tracer injection. Early maximum standardized uptake value (SUVE), delayed maximum standardized uptake value (SUVD), difference between early and delayed maximum standardized uptake value (D-SUVmax), and retention index (RI) were calculated for each duodenal lesion. Receiver operating characteristic analysis (ROC) was performed to evaluate the discriminating validity of the parameters.There were 32 malignant and 18 benign focal 18F-FDG uptake duodenal lesions. The values of SUVE, SUVD, and D-SUVmax were significantly different between malignant and benign lesions (12.5 ± 6.3 vs 5.8 ± 1.2, 13.5 ± 6.5 vs 5.5 ± 1.1 and 0.3 ± 0.8 vs 1.0 ± 1.0, respectively). The areas under the curves (AUCs) of SUVE, SUVD, D-SUVmax were 0.932, 0.964 and 0.707, respectively. There was no significantly difference between SUVE and SUVD based on AUC. In detecting malignant lesions, SUVE=6.9 yielded a sensitivity of 88.9% and specificity of 84.4%, SUVD=7.2 yielded a sensitivity of 94.6% and specificity of 90.6%, D-SUVmax=0.5 yielded a sensitivity of 72.2% and specificity of 68.8%. SUVD was the best diagnostic indicator, regarding specificity and specificity.SUVE and SUVD had good sensitivity, specificity for differentiating duodenal lesions. But there was no significantly difference between diagnostic value of SUVE and SUVD. 18F-FDG uptake patterns are helpful for differentiating benign and malignant duodenal lesions.