The purpose of our study was to explore the difference between isocitrate dehydrogenase (IDH)-1/2 gene mutation-positive and -negative high-grade gliomas (HGGs) using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. We enrolled 52 patients with histopathologically confirmed HGGs with IDH1/2 (P) (n = 16) or IDH1/2 (N) (n = 36). Histogram parameters of ADC and nCBV maps were correlated with gene mutations by using the unpaired student's t test and multivariable stepwise logistic regression analysis. The mean ADC value was higher in the IDH1 (P) group than IDH1 (N) (1,282.8 vs. 1,159.6 mm(2)/s, P = .0113). In terms of the cumulative ADC histograms, the 10th and 50th percentile values were also higher in the IDH1 (P) than IDH1 (N) (P = .0104 and .0183, respectively). We observed a higher 90th percentile value (3.121 vs. 2.397, P = .0208) and a steeper slope between the 10th (C10) and 90th (C90) of cumulative nCBV histograms (0.03386 vs. 0.02425/%, P = .0067) in the IDH1 (N) group. Multivariate analysis showed that the mean ADC mean value (P = .0048), the C90 value (P = .0113), and the slope between C10 and C90 (P = .0049) were the significant variables in the differentiation of IDH1 (P) from IDH1 (N). In conclusion, histogram analysis of ADC and nCBV maps based on entire tumor volume can be a useful tool for distinguishing IDH1 (P) and IDH1 (N), and it predicts that IDH (P) tumors have a more heterogeneous microenvironment than IDH (N) ones.