BACKGROUND: A growing body of evidence supports the use of multigene signature panels (MSPs) in predicting recurrence risk in patients with invasive breast cancer. This study aimed to evaluate trends in MSP use over time and the effect of MSPs on administration of postoperative chemotherapy. STUDY DESIGN: The National Cancer Database was queried for all women with invasive breast cancer who underwent resection between 2011 and 2014 and had information about performance of an MSP, hormone receptor status, and receipt of chemotherapy. Multigene signature panel use over time was evaluated, and patterns of use of Oncotype DX (ODX) and MammaPrint (MP) were compared. RESULTS: In a total of 476,128 patients, an MSP was obtained in 153,782 (30.2%). Multigene signature panel use increased over time and was associated with a decreased rate of chemotherapy administration (24.6% MSP vs 37.2% no MSP; p < 0.001). Oncotype DX remained the most common MSP used throughout the study period. Oncotype DX was used more commonly in stage I disease than MP, and MP was used more commonly in stage II and III disease. MammaPrint was more commonly used in hormone receptor-negative patients, human epidermal growth factor receptor 2-positive patients, and patients with positive lymph nodes. Postoperative chemotherapy was administered to a higher proportion of patients assessed with MP than with ODX (41.3% vs 23.4%, respectively; p < 0.001). CONCLUSIONS: Use of MSPs among patients with breast cancer has increased over time and is associated with a decreased use of adjuvant chemotherapy. Oncotype DX continues to be the most widely used MSP, although MP use has increased over time. Future studies are warranted to determine the optimal use of these MSPs in risk assessment and postoperative decision making.