CONTEXT: Gene expression-based prognostic assays for breast cancer are now available as commercial reference laboratory tests covered by insurance. OBJECTIVE: To provide practicing pathologists with information about the nature of these assays, differences among them, and their use by clinical oncologists in the management of patients diagnosed with breast cancer. DATA SOURCES: Review of literature and unpublished data from the National Surgical Adjuvant Breast and Bowel Project. This review focused on a general conceptual description of the technology behind these assays and differences among them to aid understanding by pathologists in practice. CONCLUSIONS: While these assays are clinically useful, they are still evolving. The future development of gene expression-based markers will need to be more clinical-context-specific to be clinically useful.