Gene expression profiling is a method to measure the expression of a large number of genes in tissue specimens simultaneously. This analytical technique is actively explored as an emerging diagnostic tool for breast cancer. An important assumption behind this research is that the constellation of multiple genes will be more predictive of clinical outcome than any single gene alone. Gene expression signatures were shown to predict prognosis of breast cancer as well as response to particular chemotherapy regimens. The first multigene predictor of prognosis after tamoxifen therapy is already commercially available in the United States. This article reviews recent advances in the clinical application of this technique to breast cancer.