A series of multigene classifiers, prognostic and predictive tests have recently been introduced as potentially useful adjuncts for the management of recently diagnosed breast cancer patients. These tests have used both slide-based methods including immunohistochemistry and fluorescence in situ hybridization and nonmorphology driven molecular platforms including quantitative multiplex real time polymerase chain reaction and genomic microarray profiling. In this review, a series of partially and completely commercialized multigene assays are compared with the standard breast cancer clinico-pathologic variables and biomarkers and evaluated as to the level of their scientific validation, current clinical utility, regulatory approval status, and estimated cost-benefit. A comparison of the Oncotype Dx and MammaPrint assays indicates that the Oncotype Dx test has the advantages of an earlier commercial launch in the US, wide acceptance for payment by third party payors, the ease of use of formalin fixed paraffin embedded tissues, a recommendation as ready for use by the American Society of Clinical Oncology Breast Cancer Tumor Markers Update Committee, a continuous rather than dichotomous algorithm, inclusion of both estrogen receptor (ER) and human epidermal growth factor receptor 2 in the mRNA profile, an ability to serve as both a prognostic and predictive test for certain hormonal and chemotherapeutic agents, demonstrated cost-effectiveness in 1 published study, and a high accrual rate for the prospective validation clinical trial (Trial Assigning Individualized Options for Treatment Rx). The MammaPrint assay has the advantages of a 510(k) clearance by the US Food and Drug Administration, a larger gene number which may enhance further utility, and the potentially wider patient eligibility including lymph node-positive, ER-negative, and younger patients being accrued into the prospective trial (the Microarray in Node-negative Disease may Avoid ChemoTherapy). A number of other assays have specific predictive goals most often focused on the efficacy of tamoxifen in ER-positive patients such as the Two-gene Ratio test and the Cytochrome P450 CYP2D6 genotyping assay.