E-selectin which is expressed on endothelial cells plays an important role in the adhesion of cancer cells to the vascular endothelium, being the ligand for a carbohydrate antigen expressed on cancer cells. In this study, the clinical usefulness of this protein was examined. E-selectin was expressed on the endothelial cells of the small vessels adjacent to the cancer nests in 63 of the 104 (60.6%) primary tumors of breast cancer. The expression of E-selectin in locations adjacent to the cancer nests was more pronounced than that in distant ones. The mean value of serum soluble E-selectin (ng/ml) was 38.3 in benign breast disease, 47.8 in those with no evidence of recurrence, 49.4 in stage I/II primary breast cancer, 75.8 in stage III/IV primary breast cancer, and 93.7 in recurrent breast cancer. The mean value of serum soluble E-selectin was 106.2 ng/ml in patients with distant metastases, and 50.4 ng/ml in those with no evidence of distant metastases. Thus, the concentration of soluble E-selectin was significantly elevated in the sera of patients with distant metastases. These findings suggested that cancer cells induced the expression of E-selectin on endothelial cells and, that serum soluble E-selectin is useful as a tumor marker having a close relationship to metastasis in breast cancer.