Three-tiered grading systems (low, intermediate, and high grade) have been proposed for neuroendocrine tumors. These classifications have not been rigorously evaluated in neuroendocrine malignancies of the digestive tract. We performed a retrospective chart analysis of 83 patients with metastatic gastroenteropancreatic neuroendocrine tumors, correlating tumor grade with overall survival. We also analyzed available biopsy specimens (on 40 patients), examining hematoxylin and eosin stains for mitotic rate and immunostaining for measurement of the Ki-67 index. Tumor grades were assigned based on the mitotic rate and the Ki-67 index, and the prognostic validity of each grading method was assessed. A highly significant correlation existed between the reported tumor grade and overall survival. Five-year survival rates for patients with low-, intermediate-, and high-grade tumors were 87%, 38%, and 0%, respectively. On biopsy specimen analysis, both mitotic rates and Ki-67 indexes correlated strongly with overall survival. We conclude that a 3-tiered grading classification for gastroenteropancreatic neuroendocrine tumors correlates with survival in the metastatic setting. Both mitotic rates and Ki-67 indexes are inversely associated with survival and can be analyzed independently for assignment of grade.