HER2 (HER-2/neu; c-erb-B2) is a 185-kd membrane receptor with tyrosine kinase activity whose gene is located on the long arm of chromosome 17 (q21). (1) Over-expression of HER2 is seen in 15% to 25% of breast cancers and is almost always associated with amplification of the HER2 gene. (2) The main methods for assessing HER2 status, therefore, include those directed at measuring the amount of receptor protein present on the cell membrane or determining amplification of the gene. Accurate testing for HER2 has become of great importance for patients with breast cancer since the availability of trastuzumab, an anti-HER2 monoclonal antibody that binds to the extracellular domain of HER2. (3) Trastuzumab has been shown to be effective only in those patients whose cancers strongly overexpress HER2 or show HER2 gene amplification. (4) Two randomized trials have demonstrated improved survival in patients with metastatic disease when treated with trastuzumab plus chemotherapy compared with chemotherapy alone. (5,6) Recent data from 4 randomized trials in the adjuvant setting have shown marked improvement in disease-free survival and overall survival when trastuzumab is added to chemotherapy. (7-11) As a result, trastuzumab therapy is being widely used in the adjuvant setting for HER2-positive breast cancer. HER2 positivity also predicts for response to adjuvant anthracycline-based chemotherapy (12) and may predict for response to adjuvant taxane therapy. (13) Thus, quality control issues and quality assurance related to HER2 testing has become increasingly important. The purpose of this study was to determine the accuracy and reproducibility of HER2 testing in 2 provinces in Canada, where testing was being performed on a population basis, to determine eligibility for trastuzumab therapy in the metastatic setting.