Background: Mucinous cystic neoplasms (MCN) of the pancreas are rare mucin-producing cystic tumors. As they harbor malignant potential, surgical resection is frequently performed. Current guidelines recommend surgery in asymptomatic patients only for MCN exceeding 4 cm. The aim of this study was to identify radiological and clinical risk factors for malignancy in a single-center cohort of MCN.Methods: All resected MCN from a single high-volume center between 2004 and 2019 were retrospectively analyzed. Patient characteristics, preoperative findings, histopathological results, and data on the postoperative course were recorded. Variables associated with malignancy were evaluated using χ 2 and Mann-Whitney U test. Receiver operating characteristic (ROC) curves were used to model predictive capabilities of preoperative tumor marker levels. Furthermore uni-and multivariate logistic regression analysis were performed for binary variables. Survival time was plotted as Kaplan-Meier curves and evaluated by log-rank test.Results: A total of 63 patients were included. Median age was 62 years; 51 (81.0%) of them were women; median tumor size was 3.5 cm (range, 0.5-18.5); 16 (25.4%) of tumors harbored invasive carcinoma and 13 presented intraepithelial dysplasia (20.6%); 7 (43.8%) invasive carcinomas were smaller than 4 cm. All malignant MCN were radiologically suspected of malignancy (calcifications, mural nodules, or wall thickness) preoperatively. Elevated levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were strongly associated with malignancy (odd's ratio 33.600; 7.000-161.270); P<0.001 and odd's ratio 19.250; 3.370-109.970; P<0.001). Other factors associated with malignancy were preoperative weight loss (P=0.015) and higher age (P=0.048). Tumor size, abdominal or back pain or jaundice showed no significant correlation to malignancy in our cohort.Conclusions: Malignant potential of MCN should not be underestimated and a close clinical and radiological follow-up is mandatory in all suspected cases. This is especially important for small lesions. Risk assessment should not rely only on tumor size but consider all clinical, radiological and laboratory findings of each case. Follow-up should be performed by experienced surgeons and radiologists in high volume centers for pancreatic surgery. Surgery should be performed in all cases in which malignancy is suspected.