Sometimes the distinction between gastric adenocarcinomas and breast carcinomas can be challenging. Hepatocyte nuclear factor 4‐alpha (HNF4A) has been suggested as a potential marker in these cases. The aim of the present work was to evaluate the role of the combined use of HNF4A and GATA3 as immunohistochemical markers in distinction between primary and metastatic breast and gastric carcinomas. This retrospective study was conducted on (81) cases divided into four groups of cohorts: primary BC (cohort I, n = 25), primary GC (cohort II, n = 23), and metastases derived from both types of tumors designated as metastasis derived from BC (cohort III‐A, n = 17) and metastasis derived from GC (cohort III‐B, n = 16). We performed immunohistochemistry analysis of HNF4A and GATA3 in all (81) cases. HNF4A expression was seen in 22 of 23 primary gastric adenocarcinomas and was absent in all 25 primary breast carcinomas (sensitivity 95.7%, specificity 100%). HNF4A was seen in 15 of 16 metastatic gastric adenocarcinomas and was absent in all 17 metastatic breast carcinomas (sensitivity 93.8%, specificity 100%). GATA3 showed 92 and 88% sensitivity, and 95.7 and 100% specificity for primary breast carcinomas and metastatic breast carcinomas, respectively. Our data confirmed the potential utility of HNF4A as a diagnostic marker and can be used as an adjunct to GATA3 as an immunohistochemical panel to differentiate between breast and gastric carcinomas.