In this study the unexpected findings from the analysis of 278 breast cancer tissue specimens are reported. A surprising strongly positive correlation between an unfavourable and a favourable prognosis with markers cathepsin D and pS2 respectively, was revealed by linear regression analysis (Pearson, Student-T-Test). In the relevant literature reviewed only one similar, although indirect, observation was found. On the other hand, a weak relationship between pS2 and ER has emerged using the same method, while the pS2/PgR association remained strong. The latter supports the hypothesis that pS2 positivity is associated with positive PgR and may be a marker of functioning ER, irrespective of ER status. These and other similar findings underline the need for a better understanding of the underlying molecular events as well as the necessity of an effective prognostic evaluation model for breast cancer.