We investigated the diagnostic importance of focal defects in the apparent diffusion coefficient (ADC)-based differentiation between lymphoma and squamous cell carcinoma (SCCs) nodes in the neck. The ADCs were analyzed for 79 lymphoma nodes from 26 patients and 88 SCC nodes from 45 patients. The ADCs of the lymphoma nodes without focal defects (0.449 +/- 0.096 x 10(-3) mm(2)/s) were significantly lower than those of the SCC nodes without focal defects (0.960 +/- 0.310 x 10(-3) mm(2)/s). However, the ADCs were not significantly different between the lymphoma and SCC nodes with focal defects (1.091 +/- 0.405 and 1.423 +/- 0.529 x 10(-3) mm(2)/s, respectively), and the differentiation was therefore ineffective. By comparison, the ADCs of the focal defects in the lymphoma nodes (1.091 +/- 0.405 x 10(-3) mm(2)/s) were significantly lower than those of the focal defects in the SCC nodes (1.905 +/- 0.640 x 10(-3) mm(2)/s). Accordingly, when the diseased nodes with or without focal defects are separately assessed using different ADC criteria (0.600 x 10(-3) mm(2)/s for entire nodes and 1.450 x 10(-3) mm(2)/s for focal defects), the overall diagnostic accuracy was significantly improved. These results suggest the importance of focal defects when differentiating lymphoma and SCC nodes based on ADC measurements.