Background: Gastric and colorectal adenocarcinomas are the second and fifth most common cancers in Iran, respectively. Prognostic factors help with the better management of patients. Objectives: The current study aimed to evaluate Cytokeratin 7 (CK7) expression in gastric and colorectal adenocarcinomas and its correlation with other prognostic factors. Methods: This cross-sectional study was performed on 75 tissue blocks from patients with gastric or colorectal adenocarcinomas. Tumor grade, tumor size, depth of invasion, and metastasis to lymph nodes were determined. Then, CK7 expression was studied using immunohistochemistry staining. The presence of CK7 was scored under high power (400x) in 1000 tumor cells, and the percentage of positive immunostaining (5%) was determined. Results: The mean age values of the patients were 62.11 ± 14.13 and 55.23 ± 14.14 years in gastric cancer and colorectal cancer groups. There was no statistically significant difference in the mean tumor size between the two groups (P = 0.678). The findings of the present study showed that in 19 cases (67.9%) of gastric cancer samples, 6 cases (42.9%) of rectal samples, and 14 cases (42.4%) of colon samples were positive for CK7. The expression of positive cytokeratin was higher than that of the rectum and colon, which was statistically significant (P = 0.034). Furthermore, there was no statistically significant relationship between the type of differentiation and lymph node involvement with cytokeratin expression in both gastric and colorectal cancers (P > 0.05). In terms of perineural involvement, there was no statistically significant relationship with both gastric and colorectal cancers (P > 0.05). Conclusions: The present study showed no association between CK7 expression and prognostic factors in colon and gastric adenocarcinomas. Given these findings and several studies in this field, it is required to perform further studies with a larger sample size to determine the exact prognostic role of this factor.