INTRODUCTION Progressive multifocal leucoencefalopathy (PML) is a subacute demielinating disease of the Central Nervous System caused by the neurotropic virus John Cunningham (JC), common in immunodeficient patients, namely in HIV infection. PML encephalic lesions have a progressive nature that needs characterization and progressive study, especially for evaluating the therapeutic response. MATERIAL AND METHODS The authors reviewed diffusion-weight MR imaging of PML lesions in four patients, characterizing the different lesional areas in DWI and ADC maps, and correlating these data with previous published studies, namely regarding histological correlation and lesion time course. RESULTS The four cases studied showed heterogeneity in DWI and ADC maps, with restriction in water diffusion in the periphery of each lesion. DISCUSSION/CONCLUSION Diffusion-weighted MR images allows characterization of PML lesions, highlighting their heterogeneity and asynchrony. These data allow important knowledge on lesions temporal evolution and treatment response.