DNA microarray platforms for gene expression profiling were invented relatively recently, and breast cancer has been among the earliest and most intensely studied diseases using this technology. The molecular signatures so identified help reveal the biologic spectrum of breast cancers, provide diagnostic tools as well as prognostic and predictive gene signatures, and may identify new therapeutic targets. Data are best presented in an open access format to facilitate external validation, the most crucial step in identifying robust, reproducible gene signatures suitable for clinical translation. Clinically practical applications derived from full expression profile studies already in use include reduced versions of microarrays representing key discriminatory genes and therapeutic targets, quantitative polymerase chain reaction assays, or immunohistochemical surrogate panels (suitable for application to standard pathology blocks). Prospective trials are now underway to determine the value of such tools for clinical decision making in breast cancer; these efforts may serve as a model for using such approaches in other tumor types.