OBJECTIVES: In this retrospective feasibility study diffusion-weighted magnetic resonance imaging (DWI) was evaluated as a potential tool for characterization of pelvic lymph nodes in patients with prostate cancer. METHODS AND MATERIALS: Twenty-nine patients with prostate cancer underwent DWI of the pelvis at 1.5T by a non breath-hold SSEPI sequence using a body phased array coil with b values of 50, 300, and 600 s/mm(2) and an additional T2-weighted sequence. A total of 118 lymph nodes (>6 mm short axis) were analyzed by measuring the ADC-value with a polygon region of interest. Feasibility for ADC-measurement was assessed by comparing the ADC-value from the automatically created ADC-map (ADC(MR_unit)) with a manually calculated ACD-value (ADC(calculated)) and by using a linear-regression model for comparison with size and standard deviation of the ADC-value. Diagnostic performance was estimated by receiver operator characteristic analysis using histologic and/or clinical follow-up as standard of reference. RESULTS: ADC(MR_unit) and ADC(calculated) showed a high correlation (r = 0.8999) with a mean percentual deviation of 6.33%. There was a highly significant difference between the mean ADC-value (x10(-3) mm(2)/s) of malignant (1.07 +/- 0.23) versus benign (1.54 +/- 0.25) lymph nodes, even in subgroup analysis for lymph nodes smaller versus larger than 10 mm. Receiver operator characteristic-analysis showed a good accuracy of the ADC-value (85.6% [101/118]; sensitivity: 86.0% [43/50]; specificity: 85.3% [53/68]) for differentiation of malignant and benign lymph nodes at a cutoff 1.30 x 10(-3) mm(2)/s. This was superior to a size-based analysis at a cutoff of 8 mm (accuracy: 66.1% [78/118]; sensitivity: 82.0% [41/50]; specificity: 54.4% [37/68]; P < 0.01). CONCLUSIONS: DWI has the potential of being an accurate technique for analysis of pelvic lymph nodes. Moreover, our preliminary results suggest that the ADC-value might perform significantly superior to size criteria to discriminate between benign and malignant lymph nodes.