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BACKGROUND: Limited data is available regarding the natural history of patients undergoing primary surveillance for intraductal papillary mucinous neoplasm (IPMN). We examine the outcome of patients selected for primary surveillance in a multidisciplinary pancreas cyst clinic. We hypothesize that symptoms, radiologic characteristics, and cytology will predict risk of developing pancreatic cancer in patients undergoing primary surveillance for IPMN.METHODS: Between January 2002 and March 2010, 522 patients were diagnosed with IPMN at a single, high volume institution. Patients were prospectively stratified as low or high oncologic risk based on analysis of demographic, clinical, radiologic, and cytopathologic data. Any patient who underwent primary operative management or less than 3 months of surveillance was excluded. RESULTS: 174(33%) patients underwent primary operative management for IPMN. Of these, 46(26%) were found to have invasive cancer. Alternatively, 292(56%) patients underwent primary surveillance for IPMN. Of these, 244(84%) were classified as low oncologic risk. Mean duration of primary surveillance was 35 (3-99) months. 28(11%) patients initially stratified as low-risk ultimately underwent pancreatic resection with a mean preoperative surveillance of 11 (4-42) months. Indications for resection were 8(29%) new main duct dilation or mural nodule, 6(21%) new or worsening symptoms, 5(18%) increasing lesion size, 2(7%) concerning cytopathology, and 7(25%) patient preference. Of the 28 patients resected after surveillance, 27(96%) demonstrated low-grade IPMN and 1(4%) high-grade dysplastic (HGD) IPMN. The patient with HGD had a family history of pancreatic cancer, but was asymptomatic, and no radiographic or cytologic indicators of malignancy. Of non-operated patients, 2(1%) developed invasive cancer at 18 and 51 months of surveillance. Neither of these patients demonstrated increasing cyst size or new concerning radiographic features prior to the diagnosis of invasive cancer. 48(16%) patients stratified as high oncologic risk were initially managed non-operatively due to age, comorbidity or patient preference. Five-year survival for this group was 62%. Of these, 13(27%) patients have died during follow-up: 2(15%) from pancreas cancer, 7(54%) from other causes, and 4(31%) unknown. CONCLUSIONS: For IPMN initially classified as low-risk, progression to pancreas cancer during surveillance was rare. Current accepted indications for resection did not forecast malignancy in this group. More accurate markers are needed to better guide IPMN surveillance. For poor operative candidates with high risk IPMN, progression to invasive cancer during surveillance was more common, though a substantial portion succumb to non-IPMN related death.