The epidemiology of gastrointestinal neuroendocrine tumors (GI-NETs) is poorly understood. Recent analyses have suggested changes in the incidence and distribution of such tumors, but have generally used data sets containing small patient numbers. We aimed to define trends in the epidemiology of GI-NETs in England over a 36-year period. We analyzed data from the national population-based cancer registry, which covers a population in excess of 50 million, over the period 1971-2006. In all, 10,324 cases of GI-NETs were identified. The overall incidence increased from 0.27 (per 100,000 per year) to 1.32 for men and from 0.35 to 1.33 for women. The anatomic distribution of tumors in the latest period analyzed was stomach 12%, small intestine 29%, appendix 38%, colon 13%, and rectum 8%. The largest absolute increase in incidence was seen in the appendix (from 0.03 to 0.41 in men; from 0.05 to 0.59 in women). The greatest relative increase was in gastric NETs, increasing 2,325% in men, and 4,746% in women. Overall, 48% of GI-NETs occurred in men. Sex-specific incidence rates for gastric, colonic, and rectal NETs are similar, whereas appendiceal lesions were more common in females, and small intestinal tumors in men. Large increases in the incidence of GI-NETs were observed, along with changes in anatomical distribution. Such changes may partly reflect changes in classification or improved detection through the increased use of endoscopy and imaging techniques. In view of the magnitude of these changes, particularly for gastric tumors, further studies to examine the underlying etiology of these changes are urgently indicated.