Neuroendocrine neoplasia (NEN) is a class of tumor/cancer characterized by shared immunophenotype and site-specific features. The NEN cancer category is identified by the expression of neuroendocrine markers in tumor cells. A common classification frame has been devised and is now adopted and implemented by the World Health Organization  (WHO) classification of tumor manuals. Two families are recognized based on differentiation status as “well-differentiated neuroendocrine tumor (NET)” and “poorly differentiated neuroendocrine carcinoma (NEC).” This classification system is adopted as such at different anatomical sites though conjugated upon site-specific descriptors recognized as the most clinically relevant. Here the common features and the site-specific intrinsic diversity are illustrated with emphasis on practical aspects directed toward clinical management. NEN cancer is discussed in detail at the most common anatomical sites, the digestive tract and pancreas, the thorax, and at rare non-endocrine anatomical sites.