The purpose of the current study was to conduct a systematic review and meta-analysis of the published literature to evaluate the diagnostic accuracy of FDG PET or PET/CT for intramedullary and extramedullary lesions in multiple myeloma. The authors conducted a systematic MEDLINE search of published articles. Two reviewers independently assessed the methodological quality of each study. We estimated pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and summary receiver operating characteristic curves in the detection of intramedullary and extramedullary lesions in multiple myeloma. Fourteen studies with a total of 395 patients met the inclusion criteria. The pooled estimates of sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FDG PET or PET/CT for the detection of extramedullary lesions in multiple myeloma were 96.0% [95% confidence interval (CI), 79.6%-99.9%], 77.8% (95% CI, 40.0%-97.2%), 3.28 (95% CI, 1.29-8.32), and 0.12 (95% CI, 0.03-0.42), respectively. The pooled estimates of sensitivity, specificity, LR+, and LR- of FDG PET or PET/CT for the detection of intramedullary lesions in multiple myeloma were 61.1% (95% CI, 43.5%-76.9%), 94.1% (95% CI, 71.3%-99.9%), 5.73 (95% CI, 1.53-21.40), and 0.43 (95% CI, 0.28-0.65), respectively. Whole-body FDG PET or PET/CT is a valuable imaging tool for the assessment of patients with multiple myeloma, especially for the appraisal of extramedullary involvement.