Objective To detect the expressions of osteopontin (OPN), breast tumor kinase (Brk), and vascular endothelial growth factor (VEGF) in the breast cancer tissue, the adjacent (2cm) normal breast tissue, and the distal(>5cm) normal breast tissue, and analyze their clinical significances. Method The immunohistochemical method was used to detect the expressions of OPN, Brk, and VEGF in the breast cancer tissue, the adjacent (2cm) normal breast tissue, and the distal (>5cm) normal breast tissue from 40 cases of breast cancer. Results ① The expressions of OPN,Brk, and VEGF in the breast cancer tissue were significantly higher than those of the adjacent (2cm) normal breast tissue and the distal (>5cm) normal breast tissue (P<0.01), the expression of Brk in the adjacent (2cm) normal breast tissue was significantly higher than that of the distal (>5 cm) normal breast tissue (P<0.05). ② In the breast cancer tissue, the OPN and Brk protein expressions were not associated with age, tumor diameter, and histological grade (P>0.05),were associated with lymph node metastasis and TNM stage (P<0.05). The VEGF protein expression was not associated with age and tumor diameter (P>0.05), but was associated with histological grade, lymph node metastasis, and TNM staging (P<0.05). ③ In the breast cancer tissue, OPN, Brk, and VEGF had positive correlation with each other (P<0.05), but not in the adjacent (2cm) normal breast tissue and the distal (>5 cm) normal breast tissue (P>0.05). Conclusions The expressions of OPN and Brk from the same signal pathway increase by turns in the distal (>5 cm) normal breast tissue, adjacent (2cm) normal breast tissue, and breast cancer tissue. OPN induced the adhesion and migration of endothelial cells to accelerate vascular repair through VEGF and Brk has correlation with the progress of tumor invasion and metastasis through participating in tumor vascularization.