The case of a female patient admitted to the hospital for a syncopal episode characterized by mental confusion, retrograde amnesia, agnosia, lack of sphincter control and behavior disorders, is presented. Cranial CT showed a frontal bihemispheric lesion. MRI completed with DWI was then performed to better define the nature of the lesion and for an in-depth diagnostic study. The diagnostic role of conventional MRI combined with DWI and the importance of the latter in the differential diagnosis between primary central nervous system lymphoma (confirmed at histology) and glioblastoma multiforme is discussed.