Abstract: Objective: To evaluate the clinical implication of variations in serum HER-2/neu extracellular domain (ECD) level before and after treatment of primary breast cancer patients. Methods: Sera from breast cancer patients before and after surgery or chemotherapy were assayed by a HER-2/ neu ECD enzyme-linked immunosorbent assay (ELISA). Results: The amount of serum HER-2/neu ECD was decreased in 74 patients (90.24%,74/82), was steady in 3 patients (3.66%, 3/82, C.V≤5%) and was increased in 5 patients (6.10 %, 5/82) after surgery. 73.3% (11/15) of patients with increasing levels of her-2/neu ECD (15/46) and 77.42% (24/31) of patients with non-increasing levels of her-2/ neu ECD (17 were decreased and 7 were unchanged, C.V≤5%) responded to chemotherapy (CR and PR)(P﹥0.05), showing no difference between the two groups. Conclusion: Longitudinal monitoring of serum HER-2/neu ECD level changes may represent a valuable tool for predicting pathological response to treatment and prognosis in patients with breast cancer.