OBJECTIVES: Recent advances in diagnostic imaging technology have been followed by an increased incidence of asymptomatic pancreatic neoplasms. Recommended clinical approaches to continued monitoring vary in frequency, invasiveness and cost. This study's objective is to compare the risks and cost implications associated with annual computed tomography (CT), empiricism (watchful waiting), endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) screening.   METHODS: Cost and accuracy information was obtained from published peer-reviewed journal articles. Empiricism serves as a baseline comparison of these procedures and includes the cost of one annual physician visit. Incremental Cost Effectiveness Ratios (ICERs) were calculated, (procedure cost / detection rate accuracy) and compared across diagnostic testing procedures. Risk was defined as the chance of missed detection due to less accurate imaging or lack of screening. RESULTS: Costs for empiricism ($82) were minimal when compared to CT ($196), EUS ($671) and MRI ($363). Although empiricism was the least expensive monitoring strategy, it was associated with the highest risk of undetected metastasizings. Of the diagnostic options, CT had the lowest diagnostic detection accuracy (74%), followed by MRI (80%) and EUS (94%). With CT as the baseline comparator, the ICERs for MRI ($2,783) and EUS ($2,200) demonstrated that both were acceptable alternatives.  CONCLUSIONS: Patients or physicians with low risk-tolerance are advised to avoid the watchful waiting approach. EUS, MRI and CT are all cost-effective diagnostic choices. Among the four choices, EUS is associated with the lowest risk and highest costs. EUS is the best monitoring choice when risk must be minimized irrespective of cost. Alternatively, annual MRI and CT scans may serve as a preferred option for patients and physicians aiming to balance risk-tolerance with procedure cost.