Introduction Patients, providers, and payers are striving to identify where value in cancer care can be increased. As part of the Choosing Wisely (CW) campaign,ASCOand the American Society for Therapeutic Radiology and Oncology have recommended against specific, yet commonly performed, treatments and procedures. Methods We conducted a retrospective analysis of Medicare claims data to examine concordance with CW recommendations across 12 cancer centers in the southeastern United States. Variability for each measure was evaluated on the basis of patient characteristics and site of care. Hierarchical linear modeling was used to examine differences in average costs per patient by concordance status. Potential cost savings were estimated on the basis of a potential 95% adherence rate and average cost difference. Results The analysis included 37,686 patients with cancer with Fee-for-Service Medicare insurance. Concordance varied by CW recommendation from 39% to 94%. Patient characteristics were similar for patients receiving concordant and nonconcordant care. Significant variability was noted across centers for all recommendations, with as much as an 89% difference. Nonconcordance was associated with higher costs for every measure. If concordance were to increase to 95% for all measures, we would estimate a $19 million difference in total cost of care per quarter. Conclusion These results demonstrate ample room for reduction of low-value care and corresponding costs associated with the CW recommendations. Because variability in concordance was driven primarily by site of care, rather than by patient factors, continued education about these low-value services is needed to improve the value of cancer care.