In 2010, the World Health Organization (WHO) classification of neuroendocrine neoplasms was reviewed and validated the crucial role of the proliferative rate. According to the WHO classification 2010, gastroenteropancreatic neuroendocrine neoplasms are classified as well‐differentiated neuroendocrine tumors (NETs) of grade 1 or 2 in up to 84%, or poorly differentiated neuroendocrine carcinomas in 6%–8%. Neuroendocrine carcinomas are of grade G. Recently, a proportion of neuroendocrine tumors presenting a number of mitoses or a Ki‐67 index higher than 20% and a well‐differentiated morphology have been identified, calling for a new category, well‐differentiated grade 3 NET (NET G‐3). Studies that have reported the characteristics of neuroendocrine neoplasms have identified more well‐differentiated NET G‐3 than neuroendocrine carcinomas. The main localizations of NET G‐3 are the pancreas, stomach, and colon. Treatment for NET G‐3 is not standardized and is balanced between G‐1/2 neuroendocrine tumor and neuroendocrine carcinoma treatments. In nonmetastatic neuroendocrine tumors, the European and American guidelines recommended a surgical resection for localized neuroendocrine neoplasm, irrespective of the tumor grading. In NET G‐3, chemotherapy is the benchmark if the main treatment goal is reduction of the tumor mass, particularly if it would allow a secondary surgery. In the present work, we review the epidemiology and make recommendations for the management of NET G‐3. Implications for Practice: Neuroendocrine tumors presenting a number of mitoses or a Ki‐67 index higher than 20% and a well‐differentiated morphology have been identified and named well‐differentiated grade 3 neuroendocrine tumors (NET G‐3). The main localizations of NET G‐3 are the pancreas, stomach, and colon. The prognosis is worse than that for NET G‐2. In nonmetastatic NET G‐3, surgery appeared to be the first option. The chemotherapy regimen in pancreatic NET G‐3 should be in line with that implemented in NET G‐1/2 when the Ki‐67 index is below 55% and should be in line with that implemented for neuroendocrine carcinoma when Ki‐67 is above 55%. 摘要 世界卫生组织(WHO)在2010年对神经内分泌肿瘤的分级进行了审查, 并确认了增殖率具有至关重要的作用。根据WHO分级2010版, 胃肠胰神经内分泌肿瘤可分为: 1级或2级高分化神经内分泌瘤(NET, 多达84%的患者为这一类型), 或者低分化神经内分泌癌(见于6%∼8%的患者)。神经内分泌癌为3级。近期研究确认了一部分出现大量有丝分裂或Ki‐67指数高于20%, 且具有高分化形态学的神经内分泌瘤, 称为3级NET(NET G3)。有研究报告了神经内分泌肿瘤的特征, 发现NET G3分化要好于神经内分泌癌。NET G3主要见于胰腺、胃和结肠。NET G3目前尚无标准治疗, 其治疗方案与NET G1/2或神经内分泌癌均有所区别。对于非转移性NET, 欧洲和美国的指南都建议无论肿瘤分级如何, 均手术切除局部NET病灶。对于NET G3, 如果治疗的主要目的是减小肿瘤体积, 尤其是意图后续手术的, 则应进行化疗。本文回顾了NET G3的流行病学, 并就其治疗管理给出了建议。The Oncologist 2016;21:1191–1199 对临床实践的提示:目前已鉴别出一种有大量有丝分裂或Ki‐67指数>20%, 且形态学分化良好的神经内分泌瘤, 命名为高分化3级神经内分泌瘤(NET G3)。NET G3主要位于胰腺、胃和结肠。NET G3预后差于NET G2。对于非转移性NET G3, 手术看来是治疗的首选措施。对于胰腺NET G3, Ki‐67<55%时化疗方案应该与NET G1/2一致, Ki‐67>55%时应与神经内分泌癌的化疗方案一致。 Neuroendocrine tumors presenting a number of mitoses or a Ki‐67 index higher than 20% and a well‐differentiated morphology have been identified and named well‐differentiated grade 3 neuroendocrine tumors (NET G‐3). The chemotherapy regimen in pancreatic NET G‐3 should be in line with that implemented in NET G‐1/2 when the Ki‐67 index is below 55% and as for the neuroendocrine carcinoma chemotherapy regimen when Ki‐67 is above 55%.