Gene-expression profiling with the use of DNA microarrays allows measurement of thousands of messenger RNA (mRNA) transcripts in a single experiment. Results of such studies have confirmed that breast cancer is not a single disease with variable morphologic features and biomarkers but, rather, a group of molecularly distinct neoplastic disorders. Profiling results also support the hypothesis that estrogen-receptor (ER)–negative and ER-positive breast cancers originate from distinct cell types and point to biologic processes that govern metastatic progression. Moreover, such profiling has uncovered molecular signatures that could influence clinical care. In this review, we summarize the results of gene-expression studies that hold the most promise to accelerate the transition between empirical and molecular medicine.