The gastrointestinal endocrine tumors are neoplastic lesions with often elusive malignant clinical behavior. The current WHO classification attempted to define a more effective approach by introducing the concepts of cell differentiation and site-specific malignancy, as well as specific criteria for carcinoma definition. WHO clinicopathological correlations embed the prognostic features: degree of cell differentiation, angioinvasion, proliferation fraction as assessed by mitotic index and Ki67, size, and functional activity. Other prognostic variables have been recognized, most of which related to specific biological features of neuroendocrine cancer cells. Nonetheless, the presence of liver or distant metastases are the prognostic variables ultimately determining the patients' fate in terms of survival and/or therapy response. A recent proposal of tumor grading and tumor, nodes, and metastases (TNM) staging aims at a simple and practical system for patients stratification. Application of such proposal should be implemented in routine clinical practice.