Secreted protein acidic and rich in cysteines-like protein 1 (SPARCL1), an extracellular matrix glycoprotein,has been implicated in the pathogenesis of several disorders including cancer. However, little is known about theexpression and significance of SPARCL1 in human breast cancer. The aim of this study was to determine theexpression pattern and clinicopathological significance of SPARCL1 in a Chinese breast cancer cohort. mRNAand protein expression of SPARCL1 in human breast cancer cell lines and breast cancer tissues was detectedusing the reverse transcription-polymerase chain reaction, real-time quantitative PCR, and Western blotting,respectively. Immunostaining of SPARCL1 in 282 Chinese breast cancer samples was examined and associationswith clinicopathological parameters were analyzed. Compared to the positive expression in immortalized humanbreast epithelial cells, SPARCL1 was nearly absent in human breast cancer cell lines. Similarly, a significantlyreduced expression of SPARCL1 was observed in human breast cancer tissues compared to that in normalbreast epithelial tissues, for both mRNA and protein levels (P < 0.001). Immunohistochemical analysis showedthat strong cytoplasmic immunostaining of SPARCL1 was observed in almost all normal breast samples (43/45)while moderate and strong immunostaining of SPARCL1 was only detected in 191 of 282 (67.7%) breast cancercases. Moreover, down-regulation of SPARCL1 was significantly correlated with lymphatic metastasis (P = 0.020)and poor grade (P = 0.044). In conclusion, SPARCL1 may be involved in the breast tumorigenesis and serve asa promising target for therapy of breast cancer.