We investigated the effect of the PAI-1 4G/5G polymorphism on incidence and progression of breast cancer as well as on PAI-1 expression in tumoral tissue. Results showed no effect on the incidence of breast cancer. Over a period of approximately five years higher event rates (metastasis, relapse, or death) were associated with the presence of 4G allels (and correlated with their number), but only in patients with more severe stage of disease (N0, T2, G2). Differences in tumoral PAI-1 levels (the more 4G allels, the higher PAI-1 levels were to be measured) were not statistically significant. However, the presence of a 5G allel was positively correlated with PAI-1 values below the commonly used cut off (14ng/mg tumoral tissue). In summary, the PAI-1 4G/5G polymorphism modulates the expression of PAI-1 in breast cancer tissue. It is relevant for the prognosis of breast cancer patients only in more severe states of disease.