Background: Neoadjuvant therapy (NAT) in breast (BC) and rectal cancer (RC) improves outcome and response to NAT is a prognostic factor. National use and response to NAT data outside clinical trials have not been reported because the cancer registry system does not record post-NAT "y" TNM stage. This study evaluated a modified registry system to collect pre-NAT and post-NAT "y" stage and define response rate and factors affecting NAT response. Methods: 1,173 hospitals with Commission on Cancer accredited programs reporting to the National Cancer Data Base (NCDB) used a modification of the Collaborative Stage Data Collection System to collect pre-NAT clinical stage and post-NAT pathologic stage (NAT chemotherapy for BC and radiation for RC) from random cases in 2007 selected from each hospital by the NCDB. Pathologic complete response (pCR) was defined as no tumor at the primary site or in lymph nodes after NAT. Factors affecting pCR were examined by logistic regression. Results: The study included 3,985 BC and 2,455 RC, comprising 44% of BC and 73% of RC treated by NAT in the NCDB. pCR occurred in 11.3% of BC and 11.2% of RC cases. Factors independently associated with pCR in BC were negative hormone receptors and clinically negative nodes before NAT; and in RC were resection of 5 or fewer lymph nodes, and treatment at NCI-designated cancer centers. Conclusions: A modified registry data system allows identification of response to NAT. Nationwide rates of pCR in BC and RC showed pCR were lower than reported in clinical trials. Key factors associated with pCR in BC were negative hormone receptors and clinically negative nodes, and in RC limited node resection and treatment at NCI-designated centers.