In clinical practice, patients often come with a pathology report and ask, “Are all G3 neuroendocrine tumors cancerous?” Not all G3 neuroendocrine tumors are cancerous, but there is a group of tumors called “highly proliferative neuroendocrine tumors”. What is a G3 neuroendocrine tumor? In terms of pathology, neuroendocrine tumors are classified into 3 grades, G1, G2 and G3, and their malignancy is ranked as G3>G2>G1. Two indicators are the main basis for neuroendocrine tumor classification, i.e. Ki67 index and tumor nuclear fission image, which represent the proliferation level of the tumor, in short, the higher the Ki67 index and tumor nuclear fission image, the faster the tumor grows. According to the current international standard, G3 neuroendocrine tumors are those with Ki67 index >20% or nuclear schizophrenia >20 per 10 high-powered fields of view, and most G3 neuroendocrine tumors are poorly differentiated, with Ki67 index >60% and very high malignancy. However, there are very few G3 grade neuroendocrine tumors that pathologically show good differentiation, Ki67 index less than 60%, and significantly lower malignancy compared to poorly differentiated G3 grade neuroendocrine carcinoma, and the treatment and prognosis of these patients are more obviously different from poorly differentiated G3 grade neuroendocrine carcinoma, and this part of G3 grade neuroendocrine tumors are pathologically specifically named as “neuroendocrine tumors with high proliferative activity”. It is evident that not all G3 grade neuroendocrine tumors are carcinomas. Clinically, highly proliferative neuroendocrine tumors are mostly found in the pancreas. How are highly proliferative neuroendocrine tumors treated? What is the prognosis? Highly proliferative neuroendocrine tumors with Ki67 index or nuclear schizograms have reached G3 grade, but the tumors are better differentiated and their biological behavior is biased toward G2 grade neuroendocrine tumors, and they respond poorly to treatment with the most commonly used chemotherapy EP regimen for G3 grade neuroendocrine cancer. The choice of treatment regimen can be similar to that of G2 grade neuroendocrine tumors. The survival time of highly proliferative active neuroendocrine tumors will be relatively longer compared to G3 grade neuroendocrine carcinoma.