Cellular adhesion molecules have been demonstrated to play an important role in the progression and metastasis of malignancies. We determined the serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin (sE-selectin) by enzyme-linked immunosorbent assay in 49 Japanese patients with metastatic breast cancer. Significantly high concentrations of sICAM-1 and sE-selectin were found in the patients with liver and/or bone metastases (both P<0.05). The mean serum sICAM-1 levels were significantly higher in patients with two or more metastatic sites compared to those with one metastatic site (P=0.001). A significant correlation was found between serum sICAM-1 (P=0.0001) and sE-selectin (P<0.0001) and the interleukin (IL)-6 levels. The patients who did not respond to chemo/ endocrine therapy showed significantly higher sICAM-1 and sE-selectin levels compared with those who responded to therapy (P=0.0004, P=0.02, respectively). Moreover, high sICAM-1 levels predicted a significantly poorer overall survival in both univariate and multivariate analyses. Our results suggest that the shedding of sICAM-1 or sE-selectin may enhance the metastatic process by escaping from host immune surveillance. The serum sICAM-1 level may help to predict the patient response to chemo/endocrine therapy and may be of prognostic significance in metastatic breast cancer patients.