Use of cancer therapies for indications not approved by the US Food and Drug Administration (FDA), also known as “off-label” use, is widely practiced in oncology care.1 Examples include bevacizumab in metastatic esophageal cancer or cetuximab in metastatic prostate cancer. In the United States, off-label use of 10 common cancer drugs accounted for nearly $5 billion in costs in 2010,1 an amount that likely substantially underrepresents current off-label spending given the escalation in oncology drug pricing and number of available products, but recent comprehensive estimates have not been published.