Gastric cancer is among the most commonly reported malignant diseases in the world and the third leading cause of death from malignant diseases worldwide. Over 90% of primary malignant stomach tumors are adenocarcinomas. The most common classification of stomach adenocarcinomas is according to histological types, first described by Lauren in 1965, into intestinal, diffuse, mixed or unclassified type. Data on the genetic changes in the diffuse type is less complete compared to intestinal type gastric cancer. One example of a well-known mutation is in the CDH1 gene, encoding the cellular adhesion molecule E-cadherin involved in the Wnt signalling pathway. The aim of this study was to demonstrate that there is a difference in the expression of the Wnt signaling pathway antagonists SFRP-1 and SFRP-3 between diffuse gastric cancers and normal tissue, as well as to determine whether there is a difference in expression between SFRP-1 and SFRP-3. In this study, 35 samples of diffuse gastric carcinoma and 35 samples of healthy stomach tissue were analyzed. Samples were obtained by endoscopic biopsy and collected from the archives of the Clinical Institute of Pathology and Cytology of the Zagreb University Hospital Centre. The slices were immunohistochemically stained with the biotin-avidin-streptavidin and horseradish peroxidase method. The primary polyclonal antibodies used were SFRP-1 and SFRP3. Quantitative analysis of SFRP-1 and SFRP-3 protein revealed a statistically significant difference in the number of SFRP-1 and SFRP-3 positive cells in healthy stomach tissue compared to tumor tissue (p <0,05). The amount of expression of SFRP proteins in healthy tissue was higher in comparison to tumor tissue. Additionally, SFRP3 expression was statistically significantly lower than SFRP1 expression in tumor tissue of the stomach, while the expression of the same proteins in healthy tissue is almost the same. In conclusion, this study has confirmed that there is a difference in Wnt-signaling pathway antagonist SFRP-1 and SFRP-3 expression between diffuse gastric carcinomas and normal stomach tissue. It was also demonstrated that there is a difference in expression between SFRP-1 and SFRP-3, which suggests that the loss of SFRP-3 expression specifically is an important characteristic of diffuse gastric cancer.