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Background & Aims: The clinical significance of “fullness” or enlargement of the pancreas (FP/EP) is not well established. The objective of this study was to report our experience with endoscopic ultrasonography (EUS) in evaluating patients referred for FP/EP found on computed tomography (CT). Methods: Patients referred to our center for EUS evaluation of FP/EP between January 1998 and December 2003 were studied. Patient demographics, clinical history, endoscopic findings, and follow-up were recorded. Multivariate analysis was used to identify predictors of pancreatic malignancy. Results: A total of 50 patients: 46% (23/50) male, mean age 59 years (range, 18–90) made up our studied population. EUS demonstrated normal findings in 42% (21/50), prominent ventral anlage (embryologic variant) in 14% (7/50), and chronic pancreatitis in 22% (11/50). In 22% (11/50), a suspicious mass was noted and fine-needle aspiration (FNA) was performed. Cytology revealed chronic inflammation in 7 patients, while adenocarcinoma was found in the remaining 4. Median follow-up was 27 months, and the diagnosis did not change in any of the 50 patients. There were no procedure-related complications. After multivariant regression analysis, the factors that were statistically associated with malignancy were a CA19-9 level >300 (P = .0002) and weight loss (P < .006). Conclusions: The majority of patients presenting with FP/EP had benign disease, but 8% had pancreatic cancer. Elevated CA19-9 and weight loss were predictive of pancreatic malignancy. EUS and EUS-FNA are safe and accurate diagnostic tests and can play an important role in evaluating patients with FP/EP. [Copyright &y& Elsevier]