Objective: To investigate the clinicopathological features and molecular phenotypes of gastric cancer with enteroblastic dif-ferentiation (GCED). Methods: A retrospective analysis of 337 patients with gastric adenocarcinoma diagnosed by the pathology de-partment of the First Affiliated Hospital of Zhejiang University in March 2013-2017 was conducted. Of them, 8 patients were diag-nosed with gastric carcinoma with intestinal blastocyte differentiation. All the patients were elderly, including 6 men and 2 women. The onset age was 68-83 years (mean 76.6 years). Two cases had serum AFP≥200 μg/L before treatment. According to the histopatho-logical morphology, the immunophenotype was analyzed by immunohistochemistry, the SALL4 gene was detected using reverse tran-scription-polymerase chain reaction (RT-PCR), and the relevant literature was reviewed. Results: Microscopically, all cases had primi-tive enteroid structures, consisting of cubic or columnar cells with clear cytoplasm, and immunohistochemical staining showed positivi-ty for either AFP and GPC3 or SALL4. The expression of SALL4 mRNA was significantly increased by RT-PCR. Follow-up from 1 to 5 years showed that 5 patients had liver and other organ metastases, 2 patients died, and 1 patient survived without a tumor. Conclusions:GCED is a rare invasive gastric adenocarcinoma with a worse prognosis than that of normal intestinal adenocarcinoma. The treatment of general intestinal adenocarcinoma has little effect. There are some characteristic changes in histology. It would be helpful for diag-nosis and differential diagnosis if clinicians are familiar with the tumor spectrum and genetic characteristics. Target therapy for an origi-nal marker, such as SALL4, has a bright future.