Amplification of HER-2/neu gene in breast cancer carries poor clinical prognosis, but its detection is important in managing the disease. Immunohistochemistry (IHC) is used traditionally to assess the HER-2/neu status, but this technique requires high quality tissue samples. Serum HER-2/neu provides an alternative non invasive option to the assessment of Her-2/neu status. To establish the reference range values of serum HER-2/neu concentration in multiethnic Malaysian women and to evaluate the association between serum HER-2/neu with the clinicopathological parameters. The study population comprised of 40 patients with breast cancer, 40 with benign breast disease (BBD) and 102 healthy volunteers. The serum- HER-2/neu concentration was measured and tissue samples from breast cancer patients were evaluated for HER-2/neu by immunohistochemistry (IHC). The mean (SD) for breast cancer, BBD, and healthy volunteers were 11.11(2.22), 8.73(2.57) and 7.88 (3.35) ng/ml, respectively in contrast to the manufacturer defined reference range of 15ng/ml. The The serum HER-2/neu concentration displayed no significant correlation with the clinicopathological parameters. No statistically significant association was noted between serum HER-2/neu concentration and tissue HER-/neu (p>0.05). Serum HER-2/neu cut off values though provided by the manufacturer was noted to be lower in our cohort, hence should ideally be determined in each population. Serum HER-2/neu assay though non invasive and cost efficient, may not yet be considered as an alternative or complementary marker to tissue HER-2/neu at this time.