The assessment of the risk of relapse is a critical need in the management strategy of breast cancer patients. To date, the most reliable prognostic factor is axillary nodal status. Several other pathological and biological parameters are currently under evaluation. Since 1982 we have been studying the prognostic role of several tumor markers in breast cancer cytosol. Elevated cytosol concentrations of tissue polypeptide antigen (TPA) have been found to have a highly significant direct correlation with both prolonged relapse-free interval (RFI) and higher survival rate. The information provided by cytosol TPA was independent of both axillary nodal status and steroid receptor content. In patients with a low risk of relapse (no axillary metastases, estrogen and progesterone receptor positive), cytosol TPA was still a significant prognostic indicator.