BACKGROUND The prognostic value of proliferating cell nuclear antigen (PCNA) has been demonstrated in recent studies of human tumors including breast cancer. METHODS PCNA immunoreactivity was assessed retrospectively in a consecutive series of 173 lymph node-negative primary breast cancer cases. The PCNA grade was determined according to estimated quartiles of nuclear immunostaining, and its association to disease-free and overall survival was studied. RESULTS PCNA grade was associated significantly with nuclear grade. On univariate analysis, PCNA grade was associated significantly with both 5-year relapse-free survival rate (Grades 1-2 = 78%; Grades 3-4 = 52%; P = 0.0117) and overall survival. On multivariate analysis, T category and PCNA were associated independently and significantly with both relapse-free and overall survival. Nevertheless, the magnitude of the association of PCNA grade to prognosis was low (relative risk of recurrence in patients with PCNA Grades 3-4 versus Grades 1-2 = 2.13), and only 24% of all relapses or 28.8% of all cancer deaths observed at 5 years occurred in patients with PCNA Grades 3-4. CONCLUSIONS The predictive value of the relationship of PCNA grade to prognosis was too low to be of value as an independent prognostic indicator.