Gastroenteropancreatic endocrine tumors (GEP ETs) constitute a spectrum of tumors that arise throughout the entire body but are drawn together under a common definition based on the expression of proteins derived from granules, vesicles, or both. GEP ET characterization is dependent on the primary tumor, and encompasses various factors: the WHO classification; hormone-related symptom recognition; hormone marker measurements; screening for inherited syndromes; staging; and somatostatin receptor characterization. Hypervascularization and somatostatin expression constitute major features of endocrine tumors that affect diagnosis, imaging, and therapy. GEP ET prognosis is characterized by its diversity, including a subgroup of patients with slowly progressive disease even at the metastatic stage. Prognosis assessment is mainly based on WHO classification and staging. A second cancer and cardiovascular comorbidity might also play a major prognostic part when present. Mastery of several key points analyzed in this Review, to be applied during the diagnostic and prognostic processes, is essential for defining a tailored therapeutic management.