Background: Annexin A2 (ANXA2) and S100A4 proteins might have important roles as biomarkers in progression and metastasis of several tumors. Aim:The aim of this study was to investigate the expression of both ANXA2 and S100A4 in endometrioid carcinoma (EC) and to correlate their expression with the clinicopathological and prognostic features including patients’ survival. Patients and methods: ANXA2 and S100A4 immunohistochemical expression was analyzed in 54 samples of EC and 20 proliferative endometrium. The overall survival (OS) and disease-free survival (DFS) were determined by Kaplan–Meier analysis. Results|: ANXA2 and S100A4 overexpression was detected in 64.8 and 74.1% of EC, respectively, which was significantly higher as compared with proliferative endometrium (P<0.001). ANXA2 expression was significantly correlated with tumor grade (P=0.011). Furthermore, a significant correlation was identified between ANXA2 and S100A4 expression and advanced International Federation of Gynecology and Obstetrics stage (P=0.004 and 0.001, respectively), myometrial invasion (P=0.03 and 0.019, respectively), and lymph node metastasis (P=0.001 and P<0.001, respectively). The expression of ANXA2 and S100A4 was positively correlated [Spearman correlation coefficient (r)=0.501,P<0.05). Kaplan–Meier survival curves revealed a significant relation between ANXA2 and S100A4 overexpression and reduced DFS (P=0.001 and P=0.015, respectively) and worse OS (P=0.008 and 0.034, respectively). Analysis of the coexpression of both markers revealed that ANXA2/S100A4 high expression group exhibited the lowest 3-year DFS and OS in patients with EC as compared with the other groups. Conclusion: Combined detection of ANXA2 and S100A4 may serve as an important index to estimate the biological behavior and predict tumor progression and prognosis of EC.