Abstract: In the past decade, with the introduction of precision medicine, the treatment of breast cancer has entered a new era. It now tends towards the de-escalation and individualization of treatment plans, aiming to minimize iatrogenic toxicity while maximizing benefits for patients without compromising survival outcomes. The 21-gene assay evaluates the expression levels of 21 genes associated with breast cancer recurrence and provides a 21-gene recurrence score (RS) to assess the risk of recurrence and potential benefit from chemotherapy in breast cancer patients. Currently, RS is recommended by multiple guidelines such as the American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN), and Chinese Anti-Cancer Association(CACA) for guiding adjuvant therapy in hormone receptor-positive (HR⁺) and human epidermal growth factor receptor 2 negative (HER2^-) early-stage breast cancer patients. However, there are still controversies surrounding its clinical application. Current research mainly focuses on optimizing RS to accurately identify patients who would benefit from adjuvant therapy, thus enabling more personalized treatment plans for breast cancer patients. This review provides an overview of the 21-gene assay, its application in HR⁺ breast cancer patients' adjuvant therapy, its impact on clinical decision-making, existing controversies regarding RS, and prospects for integrating RS with clinical pathological information. The aim is to guide further expansion of RS's application in clinical practice and achieve more precise adjuvant therapy for breast cancer patients.