PURPOSE: Serum Her-2/neu is extracted from the extracelluar domain of the Her-2/neu tyrosine kinase to serum. We evaluated the correlation between the Her-2/neu status as determined by immunohistochemical analysis (IHC) and the serum Her-2/neu concentration in a population of Korean women with breast cancer. METHODS: Serum Her-2/neu levels were examined from 254 female patients with primary breast cancer and 38 patients with metastatic breast cancer. Serum Her-2/neu levels were measured by the use of a chemiluminescence immunoassay (ADVIA centaur(R) system) during the preoperative period. The level of Her-2/neu in all of the breast cancer tissue samples was determined by IHC, and samples with an IHC grade +2 were subject to fluorescence in situ (FISH). When tissue samples exhibited IHC grade +3 or showed amplification of Her-2/neu as determined by FISH analysis, Her-2/neu was considered overexpressed. The cut-off value for serum Her-2/neu level was 10.2 ng/mL. RESULTS: The mean serum Her-2/neu level was 10.1 ng/mL in primary breast cancer samples. The serum Her-2/neu concentration significantly correlated with expression of Her-2/neu as determined by tissue IHC analysis (grade 1/3, 9.33+/-1.7 ng/mL; grade 2/3, 8.89+/-1.6 ng/mL; grade 3/3, 12.37+/-4.0 ng/mL, p<0.001). Increased serum HER-2/neu levels were associated with the lymph node status (p=0.003) and hormone unresponsiveness (p<0.001), tumor size (p<0.01) and age group (p<0.001). In metastatic breast cancer samples, the mean serum Her-2/neu level was 13.6 ng/mL. Elevated serum Her-2/neu levels were seen in 71.7% of metastatic breast cancer samples. The serum Her-2/neu level correlated with expression of Her-2/neu in metastatic tissue as determined by IHC analysis (p<0.001) rather than with the Her-2/neu status of the primary breast cancer (p=0.16) CONCLUSION: Serum Her-2/neu appears to be correlate with tissue Her-2/neu expression in primary and metastatic breast cancer where Her-2/neu is overexpressed. Further studies to determine levels of serum Her-2/neu are required to determine cuttoff values and the clinical application of the finding for breast cancer patients in Korea.