['The biological behavior of well-differentiated neuroendocrine tumors of the pancreas (PNETs) is difficult to predict. This study was designed to determine whether involvement of the main pancreatic duct (MPD) serves as a poor prognostic factor for PNETs.', 'The involvement of the MPD in PNETs was defined as ductal stenosis inside the tumor mass associated with distal MPDs more than twofold larger in diameter than the proximal ducts. We examined the correlation between MPD involvement and other clinicopathological parameters, including nodal metastasis and recurrence-free survival, in 101 patients treated consecutively at three referral centers in Japan. All patients underwent surgical resection.', 'MPD involvement was observed in 13 of the 101 cases (13%) and was associated with multiple unfavorable clinicopathological features (e.g., larger tumor size, higher histological grade, more frequent nodal metastasis, and higher recurrence rates). Patients with MPD involvement also showed significantly worse recurrence-free survival than did those without ductal involvement (P\xa0<\xa00.001), with a 5\xa0years recurrence-free rate of 41%. On multivariate analysis, MPD involvement was significantly associated with nodal metastasis [odds ratio (OR) 16; 95% confidence interval (CI) 3.8-89; P\xa0<\xa00.001] and recurrence (OR 8.0; 95% CI 1.7-46; P\xa0=\xa00.009). The radiology-pathology correlation revealed that stenosis of the MPD was due to periductal and/or intraductal tumor invasion. Cases with MPD involvement had microscopic venous invasion (P\xa0=\xa00.010) and perineural infiltration (P\xa0=\xa00.002) more frequently than did those with no ductal infiltration.'] Is pancreatic Duct Involvement in Well-Differentiated Neuroendocrine Tumors an Independent Poor Prognostic Factor?