The several options for therapy in breast cancer underline the difficulties to determine the reliable population which can be treated by a specific adjuvant therapy, and the population in which that therapy could generate morbidity, mortality, "medical surcharge" without prognosis improvement. This problem is particularly accurate in node-negative breast cancer patients. Adjuvant therapy has been proved to be more efficient, so a better definition of the prognosis and the response to adjuvant treatments could allow the selection of a sub-group of patients who can be spared chemotherapy. The quantification of the uPA/PAI-1 tumor content is one of the most relevant prognostic factors in this clinical setting. The integration of the uPA/PAI-1 prognostic information gathered in the multidisciplinary medical consensus meetings could be used to select the node-negative good/prognosis population in which chemotherapy could be avoided. This review will focus on the uPA/PAI-1 system, its biological role and its clinical implications in breast oncology. The different ways to analyse the uPA and PAI-1 content in tumor cells will be also presented and commented.