Expression cloning was used to initially isolate the reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene as a suppressor of transformation. The gene was found to encode a membrane-anchored regulator of MMPs. Experimental studies showed that RECK can suppress tumor invasion, metastasis, and angiogenesis. However, the clinical impact of RECK remains unclear. To assess the clinical significance of RECK expression in invasive breast cancer, a total of 119 patients with invasive breast cancer were retrospectively examined. Expression of RECK in tumor tissues was assessed by immunohistochemical staining. A significant correlation between RECK expression and 5-year survival rate was documented. The 5-year survival rate for patients with strong RECK expression was significantly higher than that for patients with weakly expressing tumors. Univariate and multivariate analyses confirmed that reduced RECK expression was an independent and significant factor in predicting a poor prognosis. In conclusion, RECK expression is a significant prognostic factor correlated with long-term survival for patients with invasive breast cancer. RECK expression is therefore a potentially useful prognostic marker for breast cancer. (Cancer Sci 2012; 103: 1084–1089)