Context. The prevalence of neuropathic pain in patients with cancer pain has been estimated to be around 40%. Neuropathic pain may be caused by tumor invasion and is considered as mixed nociceptive-neuropathic pain, or caused by an anticancer treatment and considered as purely neuropathic pain. The use of adjuvant analgesics in patients with cancer is usually extrapolated from their efficacy in nononcological neuropathic pain syndromes. Objectives. In this systematic review, we sought to evaluate the evidence for the beneficial and adverse effects of pharmacologic treatment of neuropathic cancer pain. Methods. A systematic review of the literature in PubMed and Embase was performed. Primary outcome measures were absolute risk benefit (ARB), defined as the number of patients with a defined degree of pain relief divided by the total number of patients in the treatment group, and absolute risk harm (ARH), defined as the fraction of patients who dropped out as a result of adverse effects. Results. We identified 30 articles that fulfilled our inclusion criteria. Overall, ARB of antidepressants, anticonvulsants, other adjuvant analgesics, or opioids greatly outweighed ARH. There were no significant differences in ARB or ARH between the four groups of medication or between patients with mixed vs. purely neuropathic pain. Because of the low methodological quality of the studies, we could not draw conclusions about the true treatment effect size of the four groups of medications. Conclusion. Once a diagnosis of neuropathic pain has been established in patients with cancer, antidepressants, anticonvulsants, or other adjuvant analgesics should be considered in addition to or instead of opioids. (C) 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.