This study was performed to determine the prognostic significance and the biological function of the structure protein keratin 18 (K18) in a group of patients with breast cancer. Paraffin sections from the primary tumors in 80 patients with breast cancer were examined for the expression of K18 by immunohistochemical staining with the monoclonal antibody CK2. The intensity of the expression measured by an immune reactive score (IRS) was compared with clinicopathological variables and follow-up data up to 10 years. Additionally K18 expression in different human breast cancer cell lines with well defined metastatic behavior were investigated to confirm the clinical data. A marked positive staining was observed in 13 (16.2%) women. Mortality rate in this group was 7.7% and 46.3% in the group with a low K18 expression. The recurrence rate was with 15.4% significantly lower in the positive group than in the negative group with 56.7%. Irrespective of the morphological tumor stage, almost all patients with strong K18 expression were still free of disease after 10 years. This clinical finding is supported by observations in cell cultures. In our collective K18 expression was found to be an independent and significant predictor for disease-free and overall survival.