Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas presents in various histopathological stages from benign to malignant lesions. The differentiation between benign and malignant IPMN is important in order to determine the treatment of the patients. However, pre-operative differentiation remains difficult. The aim of this study was to assess the utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in pre-operative differentiation of benign and malignant IPMN of the pancreas. In the present study we prospectively investigated 29 patients who underwent CT, FDG-PET, and surgery for IPMNs, followed by histopathological examination. The maximum standardized uptake value (SUVmax) was determined on FDG-PET, and differentiation of benign from malignant IPMN was tested using various SUVmax cut-off levels and various parameters derived from the CT. SUVmax was found to be significantly higher in malignant IPMNs (4.7+/-3.0) than that in benign IPMNs (1.8+/-0.3, P=0.0011). SUVmax values correlated with the histopathological types of IPMN (adenoma/borderline lesion/carcinoma in situ/invasive carcinoma) (Spearman rank correlation 0.865, P<0.0001). The specificity, sensitivity and accuracy values were best for SUVmax of 2.5 (100, 93, and 96%, respectively). The combination of mural nodule, detected on CT, and SUVmax of 2.5 offered the best diagnosis of malignant IPMN. These results suggest that FDG-PET is useful for differentiation of malignant IPMN of the pancreas, and that it should be performed in combination with other conventional imaging modalities.