Background: Well differentiated neuroendocrine tumor G3 (NET G3) patients are special parts of neuroendocrine neoplasms with a different biological behavior comparing with other G3 patients. The objective of our study was to investigate the clinical pathological features, the impact of different treatment strategies on their clinical outcomes of NET G3 and NEC in Chinese populations. Patients and Methods: We retrospectively collected 32 NET G3 patients from oncology departments of three hospitals in China and 38 neuroendocrine carcinoma (NEC) patients for comparison. Results: The most common primary site of NET G3 was pancreas (65.6%) followed by stomach and rectum. Esophageal and colon origin consisted almost one third of NEC but in none of NET G3. Significantly more NET G3 patients had hormone related symptoms and localized disease comparing with NEC. The median Ki-67 of NET G3 was 30% and median mitotic count was 12/10HPF which was lower than those of NEC and of the WHO criteria. In NET G3, overall response rate of temozolomide and capecitabine (TEMCAP) and platinum-based chemotherapy in the first-line or second-line settings was 11.8% (2/17) and 25.0% (3/12) (p=0.622), disease control rate was 81.3% (13/16) and 54.5% (6/11) (p=0.206), median progression-free survival (PFS) was 8.4 months (95% CI, 8.3-8.6) and 2.6 months (95% CI, 1.6-3.5) (p=0.061) respectively. The PFS of platinum-based therapy in NEC was 3.6 months. Conclusion: The clinical pathological features, histological characteristics and treatment response varied markedly between NET G3 and NEC. TEMCAP might be a promising treatment regimen for NET G3 patients that required further investigation.