OBJECTIVE: The aim of this study was to evaluate the outcome of patients presumed to have mucinous cysts of the pancreas who were initially selected for radiographic surveillance. METHODS: Patients with a pancreatic cyst and a measured cyst fluid carcinoembryonic antigen (CEA) ≥192 ng/mL were included. Patients were stratified by those who underwent initial resection and those who were recommended for radiographic surveillance. The natural history of these two groups was examined. RESULTS: From 1999 to 2014, 227 patients were identified who had a cyst fluid CEA ≥192 ng/mL (median 961, range 192-300,000 ng/mL). Immediate resection was performed on 63 patients (28%). Initial radiographic surveillance was recommended for 164 patients; 87% did not have main pancreatic duct dilation, and 87% met consensus criteria for radiographic surveillance. After a median follow-up of 56 months, 48 of the 164 patients (29%) had undergone resection. Ultimately, there were three cases (2%) of high-grade dysplasia and two cases of invasive carcinoma (1%) within these 164 patients selected for observation. Three of the five cases of either high-grade dysplasia or invasive carcinoma were among the 22 patients followed outside of consensus guidelines. CONCLUSIONS: Appropriately selected patients with mucinous pancreatic cysts can be safely followed with serial surveillance with a low risk of malignant progression.