The purpose of this study was to assess the value of diffusion-weighted magnetic resonance imaging (DWI) in detecting esophageal cancer and assessing lymph-node status, compared with histopathological results. DWI was prospectively performed in 24 consecutive patients with esophageal cancer, using the diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) sequence. DWIBS images were fused with T2-weighted images, and independently and blindly evaluated by three board-certified radiologists, regarding primary tumor detectability and lymph-node status. Apparent diffusion coefficients (ADCs) of the primary tumor and lymph nodes were also measured. Average primary tumor detection rate was 49.4%, average patient-based sensitivity and specificity for the detection of lymph-node metastasis were 77.8 and 55.6%, and average lymph-node group-based sensitivity and specificity were 39.4 and 92.6%. There were no interobserver differences among the three readers (P < 0.0001). Mean ADC of detected primary tumors was 1.26 +/- 0.29x10(-3) mm(2)/s. Mean ADC of metastatic lymph nodes (1.46 +/- 0.35x10(-3) mm(2)/s) was significantly higher (P < 0.0001) than that of nonmetastatic lymph nodes (1.15 +/- 0.24 mm(2)/s), but ADCs of both groups overlapped. In conclusion, this study suggests that DWI only has a limited role in detecting esophageal cancer and nodal staging.