Epidemiologic studies indicate that the overall risk of malignancy among patients with cystic fibrosis (CF) is similar to that of the general population. However, these studies and a number of case reports suggest that patients with CF may be at increased risk for the development of specific gastrointestinal cancers. Tumors of the esophagus, stomach, small and large bowels, liver and biliary tracts, and pancreas have been described. Previous reports of pancreatic cancers among patients with CF have included only adenocarcinoma in adults. This is the first description of a mucinous cystadenocarcinoma of the pancreas in an adolescent with CF. The tumor developed within a pancreatic cyst that had been initially identified 13 years before resection. Our report highlights the increased risk of pancreatic malignancy among patients who have CF and illustrates the premalignant potential of pancreatic cysts in this at-risk population. Further, it reinforces the need for careful surveillance and suggests a role for more aggressive diagnostic and therapeutic interventions for patients with atypical findings on pancreatic imaging studies.