Abstract: Objective To investigate clinicopathological characteristics and prognostic factors of patients with high-grade gastric neuroendocrine malignancies, including gastric neuroendocrine carcinomas (G-NECs) and gastric mixed adenoneuroendocrine carcinomas (G-MANECs). Methods We retrospectively analyzed the clinicopathological data of 50 patients with high-grade gastric neuroendocrine malignancies including 44 G-NECs and 6 G-MANECs in the Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University from Feb. 2009 to Aug. 2013. According to the WHO classification standard for neoplasms of digestive tract in 2010, their histology and immunohistochemical expression of synaptophysin, chromogranin A and CD56 were observed and analyzed. Prognostic factors were investigated on the basis of the follow-up information and survival analysis. Results Overall expression rates of synaptophysin, chromogranin A and CD56 were 98%, 48% and 38%, respectively. Overall median survival was 29 months; 1-, 2- and 3-years survival were 84%, 44% and 10%, respectively. Significant difference was observed between survival of G-NECs and G-MANECs (P<0.0001). Liver metastasis was found more often in G-MANECs (P=0.005). No statistical difference had been observed among the survival of subgroups of G-NECs, i.e., large-cell, small-cell and mixed NECs (P=0.9717). Conclusion The overall prognosis of patients with highgrade gastric neuroendocrine malignancies is unsatisfied, especially with G-MANECs which present more frequently with liver metastasis.