Progressive multifocal leukoencephalopathy (PML) is a rare but devastating disease in acquired immuno deficiency syndrome (AIDS) patients. PML in HIV/AIDS is rare in India and literature is limited. We are reporting a case of probable AIDS-related PML from Antiretroviral Therapy (ART) Centre Jabalpur. It was our first case of PML (possible) in 3194 registered HIV patients taking ART since 2006.