Diffusion-weighted imaging (DWI) is considered to be a useful biomarker to characterize the cellularity of lesions, yet its application in the thorax to evaluate anterior mediastinal lesions has not been well investigated. The aims of our study were to describe the magnetic resonance (MR) characteristics of anterior mediastinal masses and to assess the role of apparent diffusion coefficient (ADC) value in distinguishing benign from malignant lesions of the anterior mediastinum. We conducted a retrospective cross-sectional study including 55 patients with anterior mediastinal masses who underwent preinterventional MR scanning with the following sequences: T1 VIBE DIXON pre and post-contrast, T2 HASTE, T2 TIRM, DWI-ADC map (b values of 0 and 2000 sec/mm2). The ADC measurements were obtained by two approaches: hot-spot ROI and whole-tumor histogram analysis. The lesions were grouped by three distinct ways: benign versus malignant, group A (benign lesions and type A, AB, B1 thymoma) versus group B (type B2, B3 thymoma and other malignant lesions), lymphoma versus other malignancies. The study was composed of 55 patients, with 5 benign lesions and 50 malignant lesions. The ADCmean, ADCmedian, ADC10, ADC90 in the histogram-based approach and the hot-spot-ROI-based mean ADC of the malignant lesions were significantly lower than those of benign lesions (P values< 0.05). The hot-spot-ROI-based mean ADC had the highest value in differentiation between benign and malignant mediastinal lesions, as well as between group A and group B; the ADC cutoffs (with sensitivity, specificity) to differentiate malignant from benign lesions and group A from group B were 1.17 x 10-3 mm2/sec (80%, 80%) and 0.99 x 10-3 mm2/sec (78.4%, 88.9%), respectively. The ADC values obtained by using the hot-spot-ROI-based and the histogram-based approaches are helpful in differentiating benign and malignant anterior mediastinal masses.