OBJECTIVE To explore the clinical significance of detection of cytokeratin 19 (CK19) mRNA and carcinoembryonic antigen (CEA) mRNA expression in the diagnosis of micrometastasis in the peripheral blood of patients with breast cancer, and the relationship with other clinicopathological characteristics. METHODS Peripheral blood samples were collected from 28 normal female healthy volunteers, 20 patients with benign breast disease, and 108 patients with breast cancer (88 had undergone operation and 20 with metastasis). Real-time quantitative PCR was used to detect the mRNA expression of CK19 and CEA in the peripheral blood. RESULTS mRNA expression was negative in the blood samples from the 28 normal volunteers for both CK19 and CEA. None of the 20 patients with benign breast disease was positive for CEA mRNA, but one was positive for CK19 mRNA (5%). Of the 108 patients with breast cancer, 26 (24.1%) were positive for CK19 mRNA, 23 (21.3%) were positive for CEA mRNA, and 15 (13.9%) were positive for both CK19 mRNA and CEA mRNA. The positive rates of CK19 mRNA and/or CEA mRNA of the metastatic breast cancer patients were higher than those of the operable breast cancer patients. Statistically significant differences in tumor size, clinical stage, and expression levels of k(i)67, variant exon 6 containing isoforms of CD44 (CD44v6), and vascular endothelial growth factor (VEGF) were found between the operable breast cancer patients with micrometastasis in peripheral blood and the patients without micrometastasis (all P < 0.05). And there was no statistically significant difference between the two groups in age, tumor location, pathological histological type, nodal metastasis, and expression levels of estrogen receptor (ER), pregnant receptor (PR), CerbB2, and matrix metalloproteinase-9 (MMP9) (all P > 0.05). Multivariate analysis showed that tumor size, clinical stage, expressions of ki67, CD44v6, and VEGF were associated with micrometastasis in peripheral blood. CONCLUSIONS The combined detection of CK19 and CEA mRNA raises the detection rate of micrometastasis in the peripheral blood of breast cancer patients. Tumor size, clinical stage, expressions of ki67, CD44v6, and VEGF are effective predictors of micrometastasis in the peripheral blood of breast cancer patients.