Hypothesis: Laparoscopic ultrasound examination combined with biopsy of the cystic wall and aspiration of cystic fluid improves differential diagnosis of pancreatic cystic lesions contributing to surgical decision making. Study Design: A prospective evaluation of the impact of laparoscopic ultrasound on surgical decision making in patients with pancreatic cysts. Setting: A general community hospital; the department of surgery serves as referral for pancreatic surgery. Patients: During a 36-month period, 15 patients with pancreatic cystic lesions were prospectively evaluated by laparoscopy and laparoscopic ultrasound with ultrasound-guided biopsy of the cystic wall and aspiration of cystic fluid for cytologic study, viscosity, and determination of levels of amylase and tumor markers (carcinoembryonic antigen, cancer antigen 19.9). Results: Laparoscopic ultrasound contributed new, additional data in 8 patients (53%) when compared with compiled imaging data obtained by conventional ultrasound, computed tomography, magnetic resonance imaging, and endoscopic ultrasound. A solid cystic component was detected in 6 patients and additional small (<1 cm) cysts in 3 patients. Amylase and tumor marker levels, biopsy of the cystic wall, and cytologic examination had significant impact on surgical decision making in 6 patients. Nine patients underwent resection of the cystic lesion. Three patients diagnosed as having benign cysts had laparoscopy with laparoscopic ultrasound only. Three patients with suspicious lesions refused surgery. Laparoscopic ultrasound predicted correctly the nature of the cyst in 7 of 9 surgically treated patients (sensitivity, 78%). Two patients with serous cystadenoma had high revels of tumor markers (false-positive). Conclusion: Although a rather invasive procedure that requires general anesthesia and hospitalization, laparoscopy with laparoscopic ultrasonography was found to significantly contribute to the differential diagnosis of pancreatic cystic lesions.