The objective of this study was to examine the tumor spatial heterogeneity in myxoid-containing soft-tissue tumors (STTs) using texture analysis of diffusion-weighted imaging (DWI). A total of 40 patients with myxoid-containing STTs (23 benign and 17 malignant) were included in this study. The region of interest (ROI) was manually drawn on the apparent diffusion coefficient (ADC) map. For texture analysis, the global (mean, standard deviation, skewness, and kurtosis), regional (intensity variability and size-zone variability), and local features (energy, entropy, correlation, contrast, homogeneity, variance, and maximum probability) were extracted from the ADC map. Student's t-test was used to test the difference between group means. Analysis of covariance (ANCOVA) was performed with adjustments for age, sex, and tumor volume. The receiver operating characteristic (ROC) analysis was performed to compare diagnostic performances. Malignant myxoid-containing STTs had significantly higher kurtosis (P = 0.040), energy (P = 0.034), correlation (P<0.001), and homogeneity (P = 0.003), but significantly lower contrast (P<0.001) and variance (P = 0.001) compared with benign myxoid-containing STTs. Contrast showed the highest area under the curve (AUC = 0.923, P<0.001), sensitivity (94.12%), and specificity (86.96%). Our results reveal the potential utility of texture analysis of ADC maps for differentiating benign and malignant myxoid-containing STTs.