Solid pseudopapillary tumors of the pancreas (SPT) are rare neoplasms, and the natural history is poorly defined. The aim of this study was to define the natural history and compare patient and tumor factors between patients with malignant and non-malignant disease. Data for all patients with SPT who underwent surgical exploration at MSKCC between 1987 and 2009 were collected and analyzed. Patient, tumor, treatment, and survival variables were examined. Malignant tumors were defined as any tumor that was locally unresectable, metastatic, or recurrent. Differences between groups were analyzed by Fisher’s exact, chi-squared, Wilcoxon, and log-rank tests. Forty-five patients had an SPT during the study period. Median age was 38 years (10–63) and 38 (84%) were women. At the time of diagnosis, 38 were symptomatic, with the most common symptom being abdominal pain (n = 35). The most frequent imaging characteristic was a solid and cystic tumor (n = 29), most commonly located in the tail of the pancreas (n = 23). Resection of the primary tumor (n = 41) (41/2,919 = 1.4% of all resections) included distal pancreatectomy in 26, pancreatoduodenectomy in 11, central pancreatectomy in two, and enucleation in two. Nine patients had malignant disease defined by a locally unresectable tumor in three, liver metastases in three, locally unresectable tumor and liver metastases in one, local recurrence and liver metastases in one, and local recurrence in another. Patients with malignant disease presented with larger tumors (7.8 vs. 4.2 cm) (p < 0.005). After median follow-up of 44 months, 34 patients were without evidence of disease, four patients were alive with disease, three patients died of disease, and four patients died of other causes. These results demonstrate that SPT occurs in young women, and the majority of patients will experience long-term survival following resection. The only feature associated with malignant disease was tumor size at presentation. The majority of patients are alive at last follow-up, and a low percentage experienced disease recurrence or death from disease.