The FDA’s 2012 risk evaluation and mitigation strategy is a major step toward systematically reducing the inherent risks of chronic opioid therapy for pain, but does not distinguish between risks related to sources of pain. This article discusses the effect of risk mitigation in the treatment of cancer pain, with a focus on pretreatment screening and ongoing monitoring in this patient population that often requires pain management at some time during cancer treatment. Experience with screening, risk stratification, and interventions at one cancer center is shared, along with some recommendations for practice. A new screening checklist is proposed that summarizes known risk factors. Patients with cancer are not protected from the problems of opioid abuse/misuse, and the multidisciplinary cancer treatment team should coordinate an evaluation of risk and the monitoring of aberrant behaviors as part of the comprehensive care plan.