Background: A number of diagnostic tests are required for the detection and management of cancer. Most imaging modalities such as computerized tomography (CT) are anatomical. However, positron emission tomography (PET) is a functional diagnostic imaging technique using compounds labelled with positron-emitting radioisotopes to measure cell metabolism. It has been a useful tool in studying soft tissues such as the brain, cardiovascular system, and cancer. The aim of this systematic review is to critically summarize the health economic evidence of oncologic PET in the literature. Methods: Eight electronic databases were searched from 2005 until February 2010 to identify economic evaluation studies not included in previous Health Technology Assessment (HTA) reports. Only full health economic evaluations in English, French, or German were considered for inclusion. Economic evaluations were appraised using published quality criteria for assessing the quality of decision analytic models. Given the variety of methods used in the health economic evaluations, the economic evidence has been summarized in qualitative form. Results: From this new search, 14 publications were identified that met the inclusion criteria. All publications were decision analytic models and evaluated PET using Fluorodeoxyglucose F18 (FDG-PET). Eight publications were cost-effectiveness analyses; six were cost-utility analyses. The studies were from Australia, Belgium, Canada, France, Italy, Taiwan, Japan, the Netherlands, the United Kingdom, and the United States. In the base case analyses of these studies, cost-effectiveness results ranged from dominated to dominant. The methodology of the economic evaluations was of varying quality. Cost-effectiveness was primarily influenced by the cost of PET, the specificity of PET, and the risk of malignancy. Conclusions: Owing to improved care and less exposure to ineffective treatments, personalized medicine using PET may be cost-effective. However, the strongest evidence for the cost-effectiveness of PET is still in the staging of non-small cell lung cancer. Management decisions relating to the assessment of treatment response or radiotherapy treatment planning require further research to show the impact of PET on patient management and its cost-effectiveness. Because of the potential for increased patient throughput and the possible greater accuracy, the cost-effectiveness of PET/CT may be superior to that of PET. Only four studies of the cost-effectiveness of PET/CT were found in this review, and this is clearly an area for future research.