Objective: To investigate the expression of Bmi-1 and Mel-18 in breast cancer tissue and their clinical significance. Methods: The gene and protein expression in malignant (40 cases), benign (20 cases) and normal (20 cases) breast tissues were determined by RT-PCR and immunohistochemical method, respectively. The Bmi-1 and Mel-18 expression status and their correlationship in breast cancer tissue, and the relations of their expressions with the clinicopathologic factors were analyzed. Results: Both mRNA and protein positive expression of Bmi-1 increased significantly and successively in normal, benign and malignant breast tissues (all P<0.05), while those of the Mel-18 showed a roughly opposite tendency (no significant difference between normal breast tissue and benign breast lesion). There was a significant negative correlation between Bmi-1 and Mel-18 expression at either mRNA or protein level in breast cancer tissue (r=–0.317, P=0.023 and r=–0.413, P=0.008). The mRNA and protein levels of both Bmi-1 and Mel-18 were significantly related to the lymph node metastasis and clinical stage (all P<0.05), but not associated with the age, menstrual status, tumor size and histologic classification of the patients (all P>0.05). Conclusion: The increased Bmi-1 expression along with decreased Mel-18 expression may probably be important biological markers for malignant transformation of breast tissue or invasion and metastasis of breast cancer.