The authors report on the first case of corpus callosum glioblastoma multiforme (GBM) with diffusion-weighted (DW) magnetic resonance (MR) imaging findings that mimicked those for lymphoma but with MR spectroscopy results absent of lymphoma characteristics. This 68-year-old man presented with rapid, progressive impairment in short-term memory as well as slow responses and a change in his personality within 3 weeks of admission. Results of cranial computed tomography revealed a slightly hyperdense corpus callosum tumor with bihemispheric involvement. Magnetic resonance images showed a homogeneous mass with strong enhancement. The mass showed water restriction on DW MR images and apparent diffusion coefficient (ADC) maps but no markedly elevated lipid resonance on MR spectroscopy. The patient underwent tumor resection. Results of pathological studies with immunohistochemical analysis confirmed that the lesion was GBM. Diffusion-weighted MR imaging together with ADC mapping and MR spectroscopy was reported to be useful in differentiating GBM and primary brain lymphoma. The lymphomas were hyperintense to gray matter on DW MR images and isointense to hypointense on ADC maps because of water restriction. In contrast, the GBMs were hyperintense to gray matter on both DW MR images and ADC maps because of the T2 shine-through effect. On MR spectroscopy, lipid resonance was markedly elevated in lymphoma but only slightly elevated in GBM.