Accurate determination of the status of the type I receptor tyrosine kinase HER-2 in breast carcinomas provides significant insight into patient prognosis and may also inform selection of chemotherapeutic and hormonal treatments. At present, however, the single most important application of HER-2 testing is in the selection of patients for treatment with targeted therapies such as Herceptin. Although, based on current literature, fluorescence in situ hybridization (FISH) detection of HER-2 gene amplification may provide more accurate information in this context, this method is not yet widely available. Therefore, screening by immunohistochemistry (IHC) for HER-2 protein, backed by rigorous quality controls and FISH testing of equivocal cases with intermediate staining intensity, remains the current practice. In laboratories with highly standardized testing and quality assurance procedures, this protocol appears highly effective. Improvements in fixation procedures, standardization of antibodies, and use of automated image analysis may all increase the precision of IHC testing. However, on the basis of current data, there is a case to be made for the wider implementation of FISH testing to determine HER-2 status in breast cancer. Copyright © 2003 John Wiley & Sons, Ltd.