The role of insulin-like growth factor binding protein 5 (IGFBP5) in tumorigenesis and development of cancer is not well-defined. IGFBP5 has been shown to either stimulate or inhibit cell proliferation via an IGF-dependent mechanism and to promote cell proliferation and migration in an IGF-independent manner. In the authors' previous study, IGFBP5 was found to be significantly up-regulated in lymph node metastases compared with their paired primary breast cancers. To further determine the role of IGFBP5 in breast cancer development and to evaluate its clinical significance in breast cancer, the mRNA expression level was detected in 30 normal breast tissues, 108 primary tumors, and 30 lymph node metastases using real time reverse transcription-polymerase chain reaction. The expression levels were correlated with several clinical parameters, including clinical stage, pathologic tumor size, axillary lymph node status, nuclear grade, estrogen receptor status, Her2 status, and local relapse or distant metastasis of the patients. As a result, the expression of IGFBP5 mRNA correlated positively with the invasion of axillary lymph nodes and the status of hormonal receptor. Furthermore, overexpression of IGFBP5 was associated with poor outcome of breast cancer patients with positive lymph nodes and negative ER. Thus, the expression level of IGFBP5 may contribute to the development of breast cancer and is a prognostic factor for breast cancer.