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Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors whose incidence has increased over recent years due to improved disease knowledge and diagnostic tools, particularly endoscopy and nuclear medicine. They frequently arise in the gastro-enteropancreatic (GEP) tract, representing approximately 2% of all malignant tumors of the GEP system. Given their rarity and clinical and biological heterogeneity, there is an urgent need for standardized guidelines for the proper management of these neoplasms, which should always be referred to tertiary referral centers. Novel research strategies are needed to better define diagnostic and therapeutic algorithms, especially for specific subgroups of poorly known tumors, including duodenal NENs and functioning tumors. Cooperation between referral centers and the creation of international disease registries should be encouraged to better understand the biology and natural history of these neoplasms and, consequently, improve their management.

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