Neuroendocrine tumors (NET) may originate in different organs, from cells embryologically different but expressing common phenotypic characteristics, such as: the immuno-reactivity for markers of neuroendocrine differentiation (defined as "pan-neuroendocrine"), the capacity to secrete specific or aspecific peptide and hormones and the expression of some receptors, that are at the basis of the current diagnostic and therapeutical approach, peculiar to these tumors. NET have been conventionally distinguished in functioning, when associated with a recognized clinical endocrine syndrome, and non-functioning. However, this terminology may be misleading, since the great majority of NET may secrete neuroendocrine peptides, which can be employed as clinical markers for both diagnosis and follow-up. On the other hand, tissue immuno-reactivity for specific hormones does not always reflect secretory activity of the tumor cells. Finally, receptors and genetic markers are acquiring a relevant role in the characterization of NET, both improving knowledge of biology and physiopathology of NET, as well as in developing specific strategies to establish an early diagnosis and targeted therapies, to adopt prophylactic strategies in familial forms, and to identify more efficacious targets for therapy in the future.