BACKGROUND: The goal of this study was to conduct a comparative analysis of whole body X-ray (WBXR) and 18F-fluoro-deoxyglucose positron emission tomography (18FDG PET) in staging and response assessment of multiple myeloma. METHODS: We performed a systematic review of studies comparing 18 FDG PET with WBXR and/ or magnetic resonance imaging in terms of sensitivity for myeloma-related bone disease at staging and during follow-up. RESULTS: Eighteen studies involving 798 patients met the inclusion criteria. The mean Quality Assessment of Diagnostic Accuracy Studies (QUADAS) score, expressed as a percentage of the maximum score, was 61%. In 7 studies (n 242 patients), concordance assessment between WBXR and 18 FDG PET scan was possible, showing a higher sensitivity of the 18 FDG PET in the detection of myeloma bone lesions in 6 studies. The only study reporting on the prognostic value of 18 FDG PET at staging found that the number of FDG-avid focal lesions was an independent prognostic parameter. In addition, the limited studies on response monitoring showed that normalization of 18 FDG PET during treatment correlated with a superior clinical outcome. CONCLUSIONS: In general, 18 FDG PET has a superior sensitivity for myeloma bone lesions compared with WBXR. Future studies have to validate the additive value of myelomarelated bone disease detected on 18 FDG PET-computed tomography (CT) in predicting outcome. Response monitoring with the use of 18 FDG PET-CT during treatment is promising, allowing more precise prediction of prognosis compared with the standard response monitoring. In view of the expanding treatment options for multiple myeloma, this may provide important information for treatment decisions in the future. Cancer 2012; 118: 1971-81. (C) 2011 American Cancer Society.