The need for accurate detection of HER2 status is becoming more apparent, as therapeutic decisions are influenced by this information in both the adjuvant and advanced-stage setting. Since the US Food and Drug Administration approved trastuzumab (Herceptin) for the treatment of metastatic breast cancer, the urgency of accurately evaluating HER2 status of breast cancer specimens, in order to identify patients who might benefit from this therapy, has increased. A wide range of assay methods are available for determining HER2 status, but immunohistochemistry followed by fluorescence in situ hybridization (FISH) is the recommended approach for ambiguous cases. FISH is not as widely available and is more costly than immunohistochemistry, but economic modeling shows that it is the most effective (and cost-effective) option.