PURPOSE: The aim of this study was to correlate the expression of pigment epithelium-derived factor (PEDF), a potent endogenous antiangiogenic molecule, with severity and prognosis in breast cancer. EXPERIMENTAL DESIGN: To investigate the gene expression profile of PEDF in human breast cancer in relation to a patient's clinical variables, we examined human breast cancer tissue (n = 119), background breast tissue (n = 33), and a range of cell lines for mRNA and protein levels of PEDF by using reverse transcription PCR, real-time quantitative PCR, immunohistochemistry, and ELISA. RESULTS: By using reverse transcription PCR, real-time quantitative PCR, immunohistochemistry, and ELISA, PEDF expression was found to be dramatically decreased in breast cancer. An overall outlook for the patients inversely correlated with PEDF mRNA levels. Exogenous PEDF inhibits endothelial tubule formation induced by breast cancer cell-conditioned medium, in vitro. CONCLUSION: These observations collectively support the hypothesis that a lack of PEDF expression is a potent factor for the enhancement of tumor growth and angiogenesis in breast cancer.