Background: Tumor size, grading and lymph node involvement as well as the estrogen (ER) and progesterone (PR) receptors are important factors in predicting risk of recurrence and responsiveness to hormone and/or chemotherapy in breast cancer. Measurement of a number of new prognostic factors such as pS2 protein, epidermal growth factor receptor (EGFR) and cathepsin D appears to provide additional information; however, no consensus exists regarding their prognostic significance. The aim of the present study was to investigate the relationship between these parameters and established prognostic factors and their value in defining prognostic subgroups. Material and Methods: The present prospective study comprised 122 patients with untreated breast cancers. pS2 protein and cathepsin D were assayed immunoradiometrically, EGFR was measured by ELISA. Steroid hormone receptors were measured using a radioligand binding assay. Results: Relating the levels of these parameters to lymph node involvement, meno-pausal status as well as tumor size, no significant association could be established. ER and PR are significantly correlated with the expression of pS2 protein but not with cathepsin D. EGFR was shown to be inversely correlated with the content of ER and PR. At a median follow-up of 15-18 months, recurrence was more common in node-negative (without adjuvant therapy) as well as in node-positive (Tamoxifen and/or CMF) tumor patients with negative status for pS2 protein and steroid hormone receptors. Conclusions: A negative status for pS2 protein seems to be associated with an increased frequency of recurrence at early follow-up. EGFR and cathepsin D did not allow prediction of early recurrence in node-negative and node-positive patients, although we cannot exclude these parameters emerging as risk factors with longer follow-up.