Objective To investigate expressions of EphA2 and EphrinA1 in invasive ductal carcinoma of breast and to explore their clinical significances. Method The protein and mRNA expressions of EphA2 and EphrinA1 in 30 breast fibroma tissues, 30 breast cystic hyperplasia tissues, and 100 invasive ductal carcinoma of breast tissues were detected by immunohistochemistry andin situ hybridization respectively, and correlation between them and relations between their expressions in invasive ductal carcinoma of breast tissues and clinicopathologic factors were analyzed. Results ① The results of the immunohistochemistry andin situ hybridization tests showed that the protein and mRNA expressions of EphA2 and EphrinA1 in the invasive ductal carcinoma of breast tissues were significantly higher than those in the breast fibroma tissue (P<0.001) and breast cystic hyperplasia tissue (P<0.001). ② The positive expressions of EphA2 and EphrinA1 protein and mRNA were associated with the lymph node metastasis, histological grade, and TNM stage (P<0.05), in other words, which in the invasive ductal carcinoma of breast patients with lymph node metastasis, high histological grade, and high TNM stage were higher. However, which were not associated with the age and the tumor diameter (P>0.05). ③ The positive protein expressions or positive mRNA expressions in the invasive ductal carcinoma of breast tissues all had positive correlations between the EphA2 and the EphrinA1 (protein:rs =0.999,P<0.01; mRNA:rs =0.942,P<0.01). Conclusions EphA2 and EphrinA1 might be involved in carcinogenesis and development procedures of invasive ductal carcinoma of breast. Combined detection of EphA2 and EphrinA1 could help to predict clinical and pathologic characteristics of invasive ductal carcinoma of breast. They might provide a new target for clinical medication, prognosis, and targeted therapy.