The recurrence score derived from the 21-gene Oncotype DX assay is both prognostic and predictive of adjuvant chemotherapy benefit in node-negative, estrogen-receptor-positive breast cancer patients treated with tamoxifen. This has led to a remarkable shift in the treatment paradigm, with a sizeable number of patients being able to avoid adjuvant chemotherapy. The recurrence score was then analyzed in a large retrospective study with node-positive, estrogen-receptor-positive patients, in which it demonstrated both prognostic and predictive abilities. This review introduces the clinical trials that validated the Oncotype DX assay in the node-negative population, highlights the studies evaluating the utility of the assay in node-positive patients, examines the impact of the assay results on treatment decisions, and discusses the health outcomes and health care expenditures associated with this assay.