Serum amyloid A (SAA) is an acute-phase inflammatory protein. A growing body of evidence supports the role of SAA in carcinogenesis and metastasis. Thus, SAA has been suggested as a biomarker for tumor progression. In this study, we detected the expression of SAA in MCF-7 human breast cancer cell lines by immunofluorescence to investigate the effect of human recombinant apo-SAA (rSAA) on MCF-7 cell lines. The expression of SAA in benign and malignant breast tissues was identified by immunochemical staining, and the association of SAA expression in breast cancer with clinicopathologic features and survival was studied. Based on the resulting data, high levels of SAA expression were detected in both the MCF-7 cell line and breast cancer tissues. In vitro, SAA induced proliferation, migration, and invasion of MCF-7 cells, and stimulated the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in a dose-and time-dependent manner. Clinically, higher SAA expression in breast cancer tissues was positively associated with tumor T stages (P<0.001), lymph node metastasis (P<0.001), body mass index (P<0.001) and menopausal status (P=0.016). After a median 49-month follow-up of 215 breast cancer patients, multivariate Cox's regression analysis confirmed that SAA expression was an independent prognostic factor of breast cancer disease-free survival (hazard ratio =4.950; 95% confidence interval: 1.078-22.731). These results indicated a prognostic value of local SAA expression for breast cancer progression and risk assessment.