Metastatic spread of cancer is the major reason for patient mortality in human breast cancer. We examined expression of claudin-16 in human breast cells and tissues to identify a possible link between expression and aggressiveness in cells and between claudin-16 levels and patient prognosis. Forced expression of claudin-16 in breast cancer cells resulted in a less aggressive phenotype and reduced in vivo tumour �volume. Claudin-16 expression was reduced in human breast cancer, particularly in patients with aggressive tumours and high mortality (Martin et al. J Cell Biochem 105:41–52,2008). This suggests that claudin-16 plays a role beyond that of an initial metastasis repressor in this cancer type.