OBJECTIVES: To reveal a radiogenomic correlation between the presence of the T2-fluid-attenuated inversion recovery resection (T2-FLAIR) mismatch sign on MR images and isocitrate dehydrogenase (IDH) mutation status in adult patients with lower-grade gliomas (LGGs). METHODS: A web-based systemic search for eligible literature up to April 13, 2021, was conducted on PubMed, Embase, and the Cochrane Library databases by two independent reviewers. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We included studies evaluating the accuracy of the T2-FLAIR mismatch sign in diagnosing the IDH mutation in adult patients with LGGs. The T2-FLAIR mismatch sign was defined as a T2-hyperintense lesion that is hypointense on FLAIR except for a hyperintense rim. RESULTS: Fourteen studies (n = 1986) were finally identified. The mean age of patients in the included studies ranged from 38.5 to 56 years. The pooled area under the curve (AUC), sensitivity, and specificity were obtained for each molecular profile: IDHmut-Codel: 0.46 (95% confidence interval [CI]: 0.42-0.50), 1% (95%CI: 0-7%), and 69% (95%CI: 62-75%), respectively; IDHmut-Noncodel: 0.75 (95%CI: 0.71-0.79), 42% (95%CI: 34-50%), and 99% (95%CI: 96-100%), respectively; IDH-Mutation regardless of 1p/19q codeletion status: 0.77 (95%CI: 0.73-0.80), 29% (95%CI: 21-40%), and 99% (95%CI: 92-100%), respectively. CONCLUSIONS: The T2-FLAIR mismatch sign was an insensitive but highly specific marker for IDHmut-Noncodel and IDH-Mutation LGGs, whereas it was not a useful marker for IDHmut-Codel LGGs. The findings might identify the T2-FLAIR mismatch sign as a non-invasive imaging biomarker for the selection of patients with IDH-mutant LGGs. KEY POINTS: • The T2-FLAIR mismatch sign was not a sensitive sign for IDH mutation in LGGs. • The T2-FLAIR mismatch sign was related to IDHmut-Noncodel with a specificity of 99%. • The pooled specificity (69%) of the T2-FLAIR mismatch sign for IDHmut-Codel was low.