BACKGROUND: This study was undertaken to determine the absolute and relative value of angiogenesis, proliferating cell nuclear antigen (PCNA) and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. PATIENTS AND METHODS: Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including angiogenesis, PCNA using per-manent-section immunohistochemistry, clinicaltumor size, histological grade (HG), tumor necrosis, lymphatic vessel invasion (LVI), histological extension, histological classification, and infiltrating growth (INF), followed for a median of 10 years (range, 1 to 20). RESULTS: Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that PCNA, clinical tumor size, HG, angiogenesis, and LVI were significantly predictive of 20-year RFS or OS. Tumor necrosis was significantly predictive of OS, not of RFS. Multi-variate analysis showed that clinical tumor size (P = 0.0003), angiogenesis (P = 0.0003), PCNA (P = 0.0064), and HG (P = 0.0401) were significant independent prognostic factors for RFS. PCNA (P< 0.0001) and clinical tumor size (P = 0.0112) were significant independent prognostic factors for OS, while angiogenesis was a borderline significant factor. CONCLUSION: PCNA and angiogenesis were important new prognostic factors in node-negative breast cancer patients.