Since the first reports with laparoscopic resection of islet cell tumors in 1996, the experience worldwide is still limited, with only short-term outcomes available. Some have suggested that a malignant tumor is a contraindication to laparoscopic resection. Aim The aim of this study was to evaluate the feasibility, safety, and long-term outcome of the laparoscopic approach in patients with functioning, nonfunctioning, or overt malignant pancreatic neuroendocrine tumor (PNT). To our knowledge this is the largest single-institution series on this subject to date. Patients and methods A total of 49 consecutive patients (43 women, 6 men; mean age 58 years, range 22-83 years) underwent laparoscopic pancreatic surgery (LPS) from April 1998 to June 2007. Preoperative localization was done by computed tomography, magnetic resonance imaging, endoscopic ultrasonography, and Octreoscan imaging. Other than 9 PNTs localized in the head of the pancreas, all tumors were located in the left pancreas. Malignancy was diagnosed based on the presence of lymph nodes or liver metastasis. There were 33 patients with functioning tumors: 4 with gastrinomas (mean size 1.2 cm), 1 with a glucagonoma (4 cm), 3 with vipomas (3.2 cm), 2 with carcinoids (5.2 cm), 20 with sporadic insulinomas (1.4 cm), 2 with insulinoma/multiple endocrine neoplasia type 1 (MEN-1) (4.4 cm), and 1 with a malignant insulinoma (13 cm). Sixteen patients had a nonfunctioning tumor (mean size 5 cm). The following techniques were performed: laparoscopic spleen-preserving distal pancreatectomy (Lap SPDP), laparoscopic distal pancreatectomy with splenectomy (Lap SxDP) and laparoscopic enucleation (Lap En)/laparoscopic excision (Lap E). Lymph node dissection was performed when malignancy was suspected (Strasberg s technique). Evaluation criteria included operative and postoperative factors, pathologic data including R0 or R1 resection (the pancreatic transection margin and all transection margins on the specimen were inked). Long-term outcomes were analyzed by tumor recurrence and patient survival. Results Four cases (8.2%) were converted to open surgery. Overall, Lap SPDP, Lap SxDP, and Lap En/Lap E were performed in 15 (33.3%), 8 (17.8%), and 22 (48.9%) patients, respectively. The operative time and blood loss was significantly lower in the Lap En group compared with the other laparoscopic techniques. The group of patients with malignant tumors undergoing Lap SxDP had a longer operating time and greater blood loss compared with the other distal pancreatectomy (Lap DP) techniques. Overall, the postoperative complications were significantly higher in the Lap En group (42.8%) than in the Lap DP (Lap SPDP+Lap SxDP) group (22%). These complications were mainly pancreatic fistula: 8.7% after Lap DP and 38% after Lap En. The overall morbidity was significantly higher after Lap SPDP (26.7%) than after Lap SxDP (12.5%) owing to the occurrence of splenic complications in the Lap SPDP group without splenic vessel preservation two of seven (28.5%). The means and ranges of hospital stay after Lap SPDP, Lap SxDP, and Lap En/Lap E were 5.9 (5-14), 7.5 (5-12), and 5.5 (5-7) days, respectively (NS). Pathology examination of the specimen showed R0 resection in all patients with malignant PNT. The mean time to resumption of previous activities for patients undergoing Lap DP or Lap En was 3 weeks. There were no postoperative (30 days) or hospital deaths. Conclusions This series demonstrates that LPS is feasible and safe in benign-appearing and malignant neuroendocrine pancreatic tumors (NEPTs). The benefits of minimally invasive surgery were manifest in the short hospital stay and acceptable pancreas-related complications in high-risk patients. LPS can achieve negative tangential margins in a high percentage of patients with malignant tumors. Although surgical cure is rare in malignant NEPTs, significant long-term palliation can be achieved in a large proportion of patients with an aggressive surgical approach.