OBJECTIVES: BTcP is associated with a number of problematic physical, psychological/emotional and social complications which themselves are not only a relevant source of additional morbidity in these patients, but are also responsible for significant economic implications, for the patient, their relatives, for the healthcare system and society. METHODS: We performed a systematic literature search of PubMed electronic database through December  2014 and February 2015. The key words included “breakthrough cancer pain” and “cost effectiveness” or “economics” or “pharmacoeconomic,” and MeSH terms included “breakthrough pain” and “neoplasms”, or “economics” or “cost-benefit analysis” . There were no language or study design restrictions. A total of 20 articles were identified. Among the 10 included studies, there were two quality improvement projects, two survey studies, three decision-analytic models, one literature review, two pharmacoeconomics studies and one health economic framework. RESULTS: BTcP is associated with increased medical costs: direct medical costs, indirect costs, intangible cost. Direct medical costs might include hospital charges, cost of analgesics and other medications, radiotherapy, surgery, and clinician time; direct non-medical costs might include the cost of gas to drive to the clinic, parking during a clinic visit, highway tolls, overnight lodging for family/caregivers, meals for caregivers. Intangible costs include the patient’s pain, suffering, depression, anxiety, loss of sleep, and fatigue, as well as the family’s and/or caregiver’s distress. CONCLUSIONS: Additional studies are needed to evaluate quality-of-life improvements and the cost-effectiveness of more systematic analgesic treatments for BTcP. By delineating all the factors describing the impact of BTcP on patients, providers, and society, a comprehensive health economic model will improve clinical decision making, optimize outcomes, and enhance satisfaction with the processes of care across all stakeholder levels. In the case of HTA in breakthrough cancer pain, ethical evaluations appear to be the most important assessment focus among the considered ones.