Abstract: Objective: To study the significance of Cripto-1, which plays an important role in Epithelial-Mesenchymal Transition (EMT), and its prognosis in breast cancer. Methods:Immunohistochemistry for Cripto- 1 was performed on205 cases of breast cancer using LSAB method. The relationship between Cripto- 1, E-cadherin (E-CD), β-catenin and various pathologic factors in breast cancer was analyzed. Additionally, the relationship between the Cripto- 1 protein and reoccur -rence, metastasis, and survival time in patients was analyzed. Results: (1) Cripto- 1 was mainly expressed in the plasma of tumor cells and the positive rate was 82.9% (170 /205 ). The expression of Cripto-1 was positively correlated with pathologic stage (r=0.418 , P=0.000 ), Her 2/neu ( r=0.223 , P=0.001 ), lymph node metastasis (r=0.293 ,P=0.000 ), extranodal extension (r=0.206 , P=0.003 ), and distant metastasis ( r=0.174 , P= 0.012 ). There was no correlation between Cripto- 1 and ER, PR, or age. There was a positive correlation between the expression of Cripto-1 and histological grade (r=0.141 , P=0.044 ) in 179 invasive ductal carcinomas. ( 2) E-CD was mainly expressed in the membrane of tumor cel ls. And β-catenin was expressed in both the membrane and the plasma of tumor cells. The expression of Cripto-1 negatively correlated with E-CD (r=- 0.324 , P=0.000 ) and posi tively correlated wi th β-catenin which was expressed in the plasma of tumor cel ls (r=0.412 , P=0.000 ). (3) Mann-Whitney test showed that the level of expression in the lymph node-positive group was higher than that in lymph node-negative group (z =- 3.465 , P=0.001 ). The expression was higher in the metastatic group than in the non-metastatic group (z=- 3.899 , P=0.000 ). Univariate Kaplan-Meier analyses revealed there was negative correlation between overexpres-sion of Cripto-1 and survival (P<0.05). Cox-regression analysis indicated that the overexpression of Cripto- 1 was an independent prognostic factor in breast cancer (HR, 2.353 ). Conclusion:Cripto-1 may, through EMT, promote invasion and me-tastasis. Moreover, overexpression of Cripto-1 may prove to be of clinical value in breast cancer as an independent prog-nostic factor for improving the estimation of prognosis and guiding therapeutic decisions.