Biomarkers are frequently used to guide decisions for treatment of early-stage estrogen (ER) and progesterone (PR) receptor-positive (ER/PR+) invasive breast cancers and have been incorporated into guidelines. The American Society of Clinical Oncology (ASCO) 2016 guideline and a 2017 update were recently published to help clinicians use the tests available. ASCO currently recommends five tests that show evidence of clinical utility based on the parameters defined in the guideline. These include the 21-gene assay (Oncotype DX), Prediction of Analysis of Microarray-50 (PAM50), 12-gene risk score (Endopredict), Breast Cancer Index (BCI), and, most recently, the 70-gene assay (Mammaprint). However, discordance is often seen when the results of these gene assays are compared in a particular patient, for a number of reasons: the assays were initially developed to answer different questions, and the molecular makeup of each signature reflects this; the patient populations that were studied also differed and may not reflect the patient being tested; furthermore, the study design and statistical analysis varied between each test, leading to different scoring scales that may not be comparable. In this review, the background on the development and validation of these assays is discussed, and studies comparing them are reviewed. To provide guidance on which test to choose, the studies that support the level of evidence for clinical utility are presented. However, the choice of a particular test will also be influenced by socioeconomic factors, clinical factors, and patient preferences. We hope that a better understanding of the scientific and clinical rationale for each test will allow patients and providers to make optimal decisions for treatment of early-stage ER/PR+ breast cancer.