This study was designed to evaluate the prognostic importance of c-erbB-2 and proliferating cell nuclear antigen (PCNA) with long-term follow-up in Japanese patients with breast cancer. Four hundred and eight patients with breast cancer were studied. We investigated 6 factors, including c-erbB-2, PCNA, lymph-node status (n), clinical tumor size (T), histological grade (HG) and lymphatic vessel invasion, followed for a median of 10 years. c-erbB-2 overexpression was found in 35.0% and PCNA in 43.1% of the carcinomas. c-erbB-2 positivity was correlated with PCNA (p < 0.0001), n (p<0.0001), T (p = 0.0016), and HG (p = 0.0110). Univariate analysis showed that c-erbB-2 was significantly predictive of 20-year overall survival (OS) (p = 0.0247), but not of 20-year relapse-free survival (RFS). PCNA was significantly associated with 20-year RFS and OS (p <0.0001, p < 0.0001, respectively). Multivariate analysis showed that PCNA was an independent prognostic factor in node-negative patients, but c-erbB-2 and PCNA were not independent prognostic indicators in all patients. Although c-erbB-2 expression and PCNA were obviously important from a biological standpoint, they were not recognized as independent molecular markers.