This study was undertaken to assess blood vessel invasion (BVI) and other histologic features to determine the best method of histologic prognosis in node-negative breast cancer patients. The prognostic significance of the clinico-pathological findings was evaluated in 70 patients with node-negative breast cancer among 135 patients operated on between 1971 and 1981. The prognostic factors investigated included BVI, peritumor lymphatic invasion, clinical tumor size, nuclear grade, histological grade, mitotic grade, and tumor necrosis. BVI was detected by factor VIII-related antigen and elastica van Gieson staining. BVI-negative patients had a 20-year cumulative survival of 93.7%, versus 74.7% for BVI-positive patients (P = 0.0294). The clinical tumor size also correlated well with prognosis (P < 0.001). However, the other histologic features did not correlate with a poor prognosis. Moreover, we retrospectively examined the effect of postoperative chemotherapy for patients with BVI and T3, and the prognosis of those given chemotherapy seemed to be better than that of those who were not. Tumors measuring more than 51 mm and BVI may thus represent adverse prognostic factors in node-negative breast cancer patients.