Objective: Successful treatment of breast cancer greatly depends on the early detection of its metastasis, there- fore a sensitive and specific biomarker for detecting dissemination of the cancer cells will help to achieve this goal. This study was to evaluate the prognostic significance of human small breast epithelial mucin (hSBEM) and CD44V6 in breast cancer. Methods: The expressions of hSBEM mRNA and CD44V6 mRNA were detected with nested reverse transcription polymerase chain reaction (nested RT-PCR) in 67 samples of breast cancer and adjacent normal breast tissue, 16 samples of breast benign lesions tissue, and 67 specimens of peripheral blood from patients with breast cancer, 16 specimens of benign breast lesions, 20 specimens of healthy volunteers, and 25 (each five cases) other carcinomas tissue samples, including those of gastric carcinoma, colorectal carcinoma, esophageal carcinoma, lung carcinoma, and ovary carcinoma, were ana- lyzed for hSBEM mRNA expression by nested RT-PCR. Results: hSBEM mRNA expression was observed in 62/67 (92.54%) of breast cancer, 14/16 (87.50%) of breast benign lesions and 59/67 (88.05%) of normal breast tissue, with no significant differences between them (P > 0.05). None of the samples from other cancer tissues were positive. In peripheral blood the expression of hSBEM mRNA was detected in 34/67 (50.75%) from patients with breast cancer, with significant increasing (P < 0.05) in the cases of metastatic disease (stage IV) and those with lymph node metastasis compared with localized disease (stage I, II and III) and without lymph node metastasis, but its expression was not found in peripheral blood of patients with benign breast lesions or healthy volunteers. Although CD44V6 mRNA was significantly higher in breast cancer than in benign breast lesions tissue and normal breast tissue, its expression in peripheral blood show no significant difference (P > 0.05) in the patients with breast cancer (82.09%), benign breast lesion (75.00%), or healthy volunteers (70.00%). The expressions of hSBEM mRNA and CD44V6 mRNA had no correlation with the age of the patients, size of primary tumor, histological type and estrogen or progestin receptor status (P > 0.05). Conclusion: hSBEM mRNA, as assessed by nested RT-PCR, shows a mammary-specific and mammary-sensitive expression, and is a sensitive indicator of hematogeneous spread of breast cancer cell, while CD44V6 shows low sensitivity and specificity in detecting dissemination of breast cancer cell in peripheral blood. hSBEM mRNA is a promising molecular biomarker for detecting breast cancer micrometastases. Objective: Successful treatment of breast cancer greatly depends on the early detection of its metastasis, there- fore a sensitive and specific biomarker for detecting dissemination of the cancer cells will help to achieve this goal. This study was to evaluate the prognostic significance of human small Methods: The expressions of hSBEM mRNA and CD44V6 mRNA were detected with nested reverse transcription polymerase chain reaction (nested RT-PCR) in 67 samples of breast cancer and adjacent normal breast tissue, 16 samples of breast benign lesions tissue, and 67 specimens of peripheral blood from patients with breast cancer, 16 specimens of benign breast lesions, 20 specimens of healthy volunteers, and 25 specimens of breast cancer colorectal carcinoma, esophageal carcinoma, lung carcinoma, and ovary carcinoma, were ana lyzed for hSBEM mRNA expression by nested RT-PC Results: hSBEM mRNA expression was observed in 62/67 (92.54%) of breast cancer, 14/16 (87.50%) of breast benign lesions and 59/67 (88.05%) of normal breast tissue with no significant differences between Of peripheral blood the expression of hSBEM mRNA was detected in 34/67 (50.75%) from patients with breast cancer, with significant increasing (P <0.05) in the cases of metastatic disease (stage IV) and those with lymph node metastasis compared with localized disease (stage I, II and III) and without lymph node metastasis, but its expression was not found in peripheral blood of patients with benign breast lesions or Although CD44V6 mRNA was significantly higher in breast cancer than in benign breast lesions tissue and normal breast tissue, its expression in peripheral blood show no significant difference (P> 0.05) in the patients with breast cancer (82.09%), benign breast lesion (75.00% of healthy volunteers (70.00%). The expressions of hSBEM mRNA and CD44V6 mRNA had no correlation with the age of the patients, size of primary tumor, histological type and estrogen or progestin receptor status (P> 0.05). Conclusion: hSBEM mRNA, as assessed by nested RT-PCR, shows a mammary-specific and mammary-sensitive expression, and is a sensitive indicator of hematogeneous spread of breast cancer cells, while CD44V6 shows low sensitivity and specificity in detecting dissemination of breast cancer cell in peripheral blood. hSBEM mRNA is a promising molecular biomarker for detecting breast cancer micrometastases.