BACKGROUND: Recently, the desmoplastic reaction has been implicated as having an important function in epithelial solid tumor biology. There have been no reports showing the relativity of invasive breast cancer and the desmoplastic reaction by a quantitative analysis of the myofibroblasts that were an important player in the desmoplastic reaction. The purpose of this study was to immunohistochemically investigate the correlation between the desmoplastic reaction and the clinicopathology of invasive breast cancer. METHODS: The study included 60 patients with a known prognosis of invasive breast cancer. We quantified the expression of α-SMA as a marker of myofibroblasts in the invasive breast cancer. After staining samples for α-SMA, their expression was extracted and quantified as a relative percentage by computer-assisted image analysis. RESULTS: There was relatively wide variation in the expression of α-SMA with the percentage of the area from 0.68 to 28.15% (mean 8.48 ± 5.40%). The metastasis group showed significantly higher α-SMA expression compared with the no metastasis group (p < 0.001). When the patients were divided into two groups according to their α-SMA expression using a cutoff point at the mean value of 8.48%, the high α-SMA group had a significantly poorer overall survival rate (p < 0.001). Multivariate analysis demonstrated that α-SMA and lymph node metastasis were identified as independent predictive factors of metastasis. CONCLUSION: Myofibroblasts represent an important prognostic factor for invasive growth that is translated into a poor clinical prognosis for patients with invasive breast cancer.