Serous cystic neoplasms of the pancreas are regarded as a benign entity with rare malignant potential. Surgical resection is generally considered curative. To perform the largest single institution review of patients who underwent surgical resection for serous cystic neoplasms of the pancreas in the hopes of guiding future management. Between June 1988 and January 2005, 158 patients with serous cystic neoplasms of the pancreas underwent surgical resection. A retrospective analysis was performed. Univariate and multivariate models were used to determine factors influencing perioperative morbidity and mortality. Major complications were defined as pancreatic fistula or anastomotic leak, postoperative bleed, retained operative material, or death. Minor complications were defined as wound infection, postoperative obstruction/ileus requiring total parenteral nutrition (TPN), delayed gastric emptying, arrhythmia, or other infection. The mean age of the patients was 62.1 years, with 75% being female. The majority of patients were symptomatic at presentation (63%), with abdominal pain as the most common symptom. Of the 158 patients, 75 underwent distal pancreatectomy, 65 underwent pancreaticoduodenectomy, nine underwent central pancreatectomy, five underwent local resection or enucleation, and four underwent total pancreatectomy. Mean tumor diameter was 5.1 cm. Mean operative time was 277 min. Mean postoperative length of hospital stay was 11 days. One patient was diagnosed at presentation with serous cystadenocarcinoma. The remaining 157 patients were initially diagnosed with benign serous cystadenoma. One of three patients with locally aggressive benign disease later presented with metastatic disease. Resection margins for all 158 patients were negative for tumor, and only one (0.6%) showed lymph node involvement. There was one intraoperative death. The incidence of major perioperative complications was 18%, whereas the incidence of minor complications was 33%. Men were significantly more likely to experience minor perioperative complications (OR = 3.74, P = 0.008), whereas patients greater than 65 years showed a trend toward fewer major complications (OR = 0.36, P = 0.09). Surgically resected serous cystic neoplasms of the pancreas are typically seen in asymptomatic women as 5 cm neoplasms and are predominantly benign. Most are resected via either a left- or right-sided pancreatectomy with low mortality risk, but with notable major or minor morbidity. Cystadenocarcinoma is a rare finding on initial resection of serous cystic neoplasms. However, initial pathology specimens exhibiting benign but locally aggressive neoplasia may indicate an increased likelihood of recurrence or metachronous metastasis, although this claim is limited by a small patient subpopulation in this study and warrants further review.