The consistency of the prognostic role of cell kinetics (evaluated as the [3H]thymidine labeling index, LI) over a period of years has been assessed in 354 patients with resectable node-negative breast cancer subjected only to Halsted or modified radical mastectomy. The risk of disease recurrence and death was proportional to LI values and the pattern was superimposable, regardless of menopausal status, in the two consecutive case series entered in this retrospective study. In particular, tumors with high LI (greater than 2.8%) had a higher 6-year probability (41% vs. 25%, P less than 0.0001) of manifesting local-regional and distant metastases and of dying (19% vs. 5%, P = 0.0005) as compared to tumors with low LI. In tumors with high LI the risk of relapse within the first 2 years from mastectomy was twofold compared to that of tumors with low LI. Multiple regression analysis showed that LI also retained its prognostic significance in both relapse-free and overall survival when tumor size and estrogen receptor status were considered. The present findings confirm that LI can substantially contribute to the selection of high risk node-negative patients who could be candidates for adjuvant chemotherapy.