Introduction. Despite various diagnostic testing and treatment options, stomach cancer ranks 5th in terms of global morbidity among all cancers. Diffuse gastric cancer occurs more frequently in younger patients and has a more aggressive course than the intestinal type. Modern ideas about the etiology, pathogenesis, and molecular structure of a tumor allow us to take a new look at diffuse gastric cancer in the light of revised classifications, recommendations, as well as approaches to the interpretation of morphological research data. Therefore, the study aimed to conduct a multifactorial analysis of patients with diffuse gastric cancer. Materials and methods. The study included 124 patients with diffuse gastric cancer. Clinical data (medi-cal histories, protocols of endoscopic and surgical operations, sex, and age groups) and the primary tumor localization were analyzed. We formed a group of 25 observations out of 124 patients. In the group, we carried out a range of diagnostic measures: histological, histochemical, immunohistochemical, and molecular assays, as well as PCR testing. Results. In the group of 124 patients, the age of men averaged 67.5 (±12.4) years and that of women, 71 (±15.41) years. The malignant tumors were more frequently detected in distal parts of the stomach. In the group of 25 patients, Helicobacter pylori were present only in 2 cases. We detected the Epstein-Barr virus in 11 patients out of 25 using real-time PCR method. A study of the immunophenotype of diffuse gastric cancer using a wide panel of antibodies demonstrated heterogeneity of expression in both components of a malignant tumor. The expression of CK7, Muc1, Muc2, and Muc5AC markers in patients with a microsatel-lite unstable molecular subtype was noteworthy. Conclusion. The immunophenotypic heterogeneity of diffuse gastric cancer requires further research. It is necessary to create a standardized pathology evaluation protocol, including molecular and immunohisto-chemical tests that is the basis for modern management of cancer patients with diffuse gastric cancer. © 2021, MDV Group. All rights reserved.