The Opioid Risk Tool (ORT) is a screening tool used to assess risk of opioid misuse by stratifying aberrant drug-seeking behaviors and/or identifying known risk factors for drug abuse. The objectives of this study were to risk stratify opioid misuse in a cancer pain population and determine the most common patient risk factors associated with misuse utilizing the ORT. This was a retrospective analysis conducted at an academic comprehensive cancer center. Patients were referred by an oncologist or hematologist to an outpatient palliative care clinic. One-hundred and fourteen patients with cancer (n = 107) or sickle cell disease (n = 7) were evaluated from July 2012 to July 2013. During the clinical interview, patients responded to a clinician administered ORT. Based on the ORT score, patients were stratified into low, moderate, or high risk for opioid misuse. Sample size included 57 men and 57 women. Sixty-five, 21, and 28 patients were deemed low, moderate, and high risk based on the ORT, respectively. The most common risk factors for opioid misuse were a history of depression (women = 32; men = 22) and family history of alcohol abuse (women = 26; men = 22). There was no difference between men and women in the prevalence of depression (P = .17) or family history of alcohol abuse (P = .57). The least common risk factor was a personal history of prescription drug abuse (n = 1) in women and history of preadolescent sexual abuse in men (n = 0). Twenty-five percent (n = 28) of the sample population were deemed high risk based on the ORT. Screening of cancer patients in the palliative care setting suggests that risk factors for opioid misuse exist. Stratifying patients based on a routine screening tool may help identify cancer patients at risk for aberrant drug behaviors.