OBJECTIVE. The purpose of this study was to determine whether lymphoma and astrocytic tumor infiltrating the corpus callosum can be reliably differentiated with measurement of water diffusivity. MATERIALS AND METHODS. Echo-planar diffusion-weighted MR images of 27 patients with glioblastoma multiforme, five patients with low-grade astrocytoma, five patients with gliomatosis cerebri, and nine patients with primary lymphoma infiltrating the corpus callosum were reviewed retrospectively. Regions of interest were drawn on apparent diffusion coefficient (ADC) maps inside the callosal tumor. ADCs were normalized by calculation of the ratio between the ADC of the tumor and the ADC of an uninvolved region of corpus callosum. RESULTS. The mean ADC of glioblastoma multiforme was 1.13 ± 0.31 (SD) × 10^–3 mm²/s, and the mean tumor to corpus callosum ADC ratio was 1.51 ± 0.46; of low-grade astrocytoma, 1.14 ± 0.23 × 10^–3 mm²/s and 1.54 ± 0.28; gliomatosis cerebri, 1.01 ± 0.20 × 10^–3 mm²/s and 1.31 ± 0.36; and lymphoma, 0.71 ± 0.13 × 10^–3 mm²/s and 0.93 ± 0.19. The difference between the mean tumor to corpus callosum ADC ratio of lymphoma and that of all grades of astrocytoma (1.48 ± 0.43) was statistically significant (p < 0.001). The optimal ADC threshold for discriminating astrocytic tumor and lymphoma was 0.90 × 10^–3 mm²/s (sensitivity, 84%; specificity, 89%). The optimal threshold for tumor to corpus callosum ADC ratio was 1.22 (sensitivity, 73%; specificity, 100%). CONCLUSION. The water diffusivity and the ADC ratio of the tumor to normal-appearing corpus callosum of astrocytic tumor differ significantly from those of lymphoma infiltrating the corpus callosum, allowing reliable differentiation of the two types of tumor.