Poorly differentiated neuroendocrine carcinomas (PDNECs) of the gastroenteropancreatic system (GEP) are a heterogeneous group of aggressive malignancies with a high propensity for distant metastases and an ominous prognosis. They have traditionally been divided into small and large cell subtypes on morphological grounds. However, histological diagnosis needs to be supported by immunohistochemistry to avoid possible misdiagnoses either with the more frequent poorly differentiated adenocarcinomas and squamous cell carcinomas or with lymphomas and mesenchymal neoplasms. Although it is well known that GEP PDNECs are associated with a poor prognosis, data from some published studies seem to suggest that there is a fraction of patients with PDNECs who have better survival than expected. GEP PDNECs are currently classified according to the criteria proposed in the 2010 WHO classification. They are simply called neuroendocrine carcinomas (NECs) and are defined by mitotic count >20 × 10 HPF and/or Ki-67 labeling index >20 %. However, a few recent papers have indicated that some NECs, as defined by the 2010 WHO scheme, do not show a poorly differentiated morphology as expected. This category seems to show a better prognosis and, especially, does not respond to cisplatin-based chemotherapy, which represents the goal standard therapeutic approach to high-grade PDNECs. In the present review, the main morphological, immunohistochemical, and prognostic features will be discussed as well as the opportunity to introduce a new category characterized by well to moderately differentiated morphology associated with high proliferation (mitotic count >20 × 10 HPF and/or Ki-67 index >20 %).