Progressive Multifocal Leukoencephalopathy is a demyelinating disease. MRI shows high signal intensity areas on T2w sequence and low intensity aeras on T1w sequence, without enhancement after intravenous contrast injection. The involvement of arcuate fiber (U fibers) creates a sharp border with the cortex. There is no mass effect. Involvement of parieto-occipital areas is frequent. The lesions may be uni or bilateral, single or multiple; bilateral lesions are asymmetric. This typical appearance on MR images occurs in 90% of the patients with PML. Some atypical patterns may occur: focal hemorrhage, atrophy, faint peripheral enhancement and involvement of deep gray matter (basal ganglia). In most cases, the clinical and MR features provide the diagnosis. The main differential diagnosis, in MRI, is HIV-leukoencephalitis, but lesions are diffuse, less intense on T2w sequence and not visible on T1, without involvement of the arcuate fibers. Stereotactic biopsy should be performed only for atypical lesions, particularly in case of predominant involvement of deep gray structures.