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Background: Positron Emission Tomography/computed tomography (PET/CT) is an imaging technique which has a role in the detection and staging malignancies (both in first diagnosis and follow-up). The finding of an unexpected region of FDG (Fluorodeoxyglucose) uptake can occur when performing whole-body FDG-PET, raising the possibility of a second primary tumor. The aim of this study was to evaluate our experience of second primary cancer incidentally discovered during PET/CT examination performed for pancreatic diseases, during the initial work-up or follow-up after surgical resection., Methods: In this study, a retrospective evaluation of a prospectively collected data base was performed. Three hundred ninety- nine patients with pancreatic pathology were evaluated by whole body PET/CT imaging from January 2004 to December 2014. Among them, 348 patients were scanned before surgical resection and 51 during the course of their follow-up (pancreatic cancer). Median follow-up time was 29 months (range 14-124)., Results: Fifty-six patients (14%) had incidental uptake of FDG in their organs: 31 patients had focal uptake and 25 showed diffuse with or without focal uptake. All patients with focal uptake were investigated, and invasive malignancy was diagnosed in 22 patients: 14 colon, 4 lung, 1 larynx, 1 urothelial, 1 breast cancer, and 1 colon metastasis from pancreatic cancer. Twenty patients underwent resection, and 6 endoscopic removal of colonic polyps. Three patients were not operated for advanced disease, and two patients did not show any pathology (PET/CT false positive). Of the 10 patients investigated for diffuse uptake, no malignancy was found; none of these patients developed a second cancer during the follow-up., Conclusions: As in other malignancies, unexpected FDG uptake can occur in patients having PET/CT investigation for pancreatic diseases. Focal uptake is likely to be a malignancy and deserves further investigations, although the stage and the poor prognosis of primary pancreatic cancer should be kept in mind. Some selected patients may benefit from the aggressive treatment of incidental lesions and show survival benefit.