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Introduction: To evaluate the value of diffusion-weighted magnetic resonance imaging compared with conventional magnetic resonance imaging (C-MRI) for the differentiation of benign from malignant lymph nodes in different regions of the body., Patients and Methods: A total of 31 patients ranging in age from 18 to 75 years (mean age: 53 years) were included in this study. The patients were examined using a 1.5-T magnetic resonance imaging system with coils chosen according to lymph node locations. Diffusion-weighted images were obtained using the single-shot echo planar sequence and had b values of 50, 500, and 1000 s/mm(2.) The apparent diffusion coefficient (ADC) values were measured from ADC maps. The correlation between the pathological diagnoses and mean ADC values in the benign and malignant lymph node groups were compared using the Mann-Whitney U-test with Bonferroni correction. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of the method., Results: The mean ADC value for benign lymph nodes was 0.97×10(-3) mm(2)/s (range: 0.6-1.2×10(-3) mm(2)/s), and the mean ADC value for malignant lymph nodes was 0.76×10(-3) mm(2)/s (range: 0.3-1.2×10(-3) mm(2)/s) (P<.001). In ROC analysis, the cut-off ADC value for malignant versus benign lymph node differentiation was 0.8×10(-3) mm(2)/s. Using an ADC value of 0.8×10(-3) mm(2)/s, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the method for differentiating between benign and malignant lymph nodes were 76.4%, 85.7%, 86.6%, 75%, and 80.6%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of C-MRI were 88.2%, 78.5%, 83.3, 84.6%, and 83.8%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of C-MRI findings suspicious for malignancy combined with the ADC values were 76.4%, 64.2%, 100%, 81.8%, and 91.6%, respectively., Conclusions: C-MRI alone remained superior to diffusion-weighted imaging (DWI) and combination C-MRI and DWI for differentiating malignant from benign lymph nodes; however, DWI and ADC calculation may play a role in lymph node characterization., (Copyright © 2015 Elsevier Inc. All rights reserved.)