The role of diffusion-weighted magnetic resonance imaging (MRI) for differentiation between various causes of cervical lymphadenopathy was evaluated. In a prospective study, 31 untreated patients (22 males and nine females, aged 5-70 years) with 87 cervical lymph nodes underwent diffusion-weighted MRI before performance of neck dissection (n=14), surgical biopsy (n=9) or core biopsy (n=8). Diffusion-weighted MR images were acquired with a b factor of 0 and 1,000 s/mm2 using single-shot echo-planar sequence. Apparent diffusion coefficient (ADC) maps were reconstructed for all patients. The signal intensity of the lymph nodes was assessed on images obtained at b=0 or 1,000 s/mm2 and from the ADC maps. The ADC value of lymph nodes was also calculated. On the ADC map, malignant nodes showed either low (n=52) or mixed (n=20) signal intensity and benign nodes revealed high (n=13) or low (n=2) signal intensity. The mean ADC value of metastatic (1.09+/-0.11x10(-3) mm2/s) and lymphomatous (0.97+/-0.27x10(-3) mm2/s) lymph nodes was significantly lower than that of benign (1.64+/-0.16x10(-3) mm2/s) cervical lymph nodes (P<0.04). When an ADC value of 1.38x10(-3) mm2/s was used as a threshold value for differentiating malignant from benign lymph nodes, the best results were obtained with an accuracy of 96%, sensitivity of 98%, specificity of 88%, positive predictive value of 98.5% and negative predictive value of 83.7%. The smallest detected lymph node was 0.9 cm. In conclusion, diffusion-weighted MRI with ADC mapping is a new promising technique that can differentiate malignant from benign lymph nodes and delineate the solid viable part of the lymph node for biopsy. This technique provides additional useful physiological and functional information regarding characterization of cervical lymph nodes.