A wide range of frequencies has been reported for blood vessel invasion (BVI) among patients with breast cancer, however, the prognostic significance of BVI remains controversial. Three hundred ninety-eight Japanese patients with breast cancer, operated on during the period between 1971 and 1987, were studied. We investigated five factors, including BVI, lymph-node status (n), clinical tumor size (T), histological grade (HG), and tumor necrosis (TN), followed for a median of 10 years. BVI was detected by hematoxylin and eosin (HE) staining and both factor VIII-related antigen and elastica van Gieson staining. BVI detected by HE staining alone was defined as BVIh. The subtypes of BVI were classified as follows: BVI e, BVI detected only by elastica van Gieson staining; BVI f, BVI detected only by factor VIII-related antigen staining; and BVI e/f, BVI detected by both factor VIII-related antigen and elastica van Gieson staining. BVI-positive tumors were defined as lesions showing BVI e, BVI f, or BVI e/f. BVI and BVIh were presented in 27.4%, 6.5% of all cases, respectively. The mean diameters of the calibers of BVI e, BVI f, and BVI e/f were 141.9 ± 80.5 μm, 61.0 ± 37.4 μm, 136.0 ± 102.0 μm, respectively (P < 0.0001). Seventy-three patients (18.3%) had recurrence and 60 patients (15.1%) died of breast cancer. Univariate analysis showed that BVIh (P < 0.0001), BVI (P < 0.0001), n, T, and HG were significantly predictive of 20-year RFS and OS. Multivariate analysis showed that BVI (P < 0.0001, P = 0.0088, respectively), n, T, and HG were all significant and independent prognostic factors for RFS and OS. On the other hand, BVIh was an independent factor for RFS (P= 0.0475), but of borderline significance for OS (P= 0.0506). When stratified by BVI, BVI e, and BVI e/f were significantly predictive of 20-year RFS or OS (P > 0.0001). We can confirm BVI, especially BVI e and BVI e/f, are significant independent prognostic factors associated with long-term survival in Japanese breast cancer patients.