PML is classically identified in patients with hematopoietic cancers, HIV infection and immunosuppressive therapy in transplant recipients. It has also been reported with the use of monoclonal therapy, autoimmune disorders, and primary immunodeficiencies. The classic presentation is characterized by subacute worsening of cognition, gait and limb ataxia, visual and motor deficits. Imaging typically shows confluent white matter lesions in the cerebral hemispheres with or without contrast enhancement. Rarely, PML can be isolated to the brainstem though other etiologies must be ruled out. An atypical clinical presentation and the lack of classic WM lesions should trigger additional investigations to rule out alternative diagnoses in patients with suspected PML. PML is an increasingly common entity due to a greater prevalence of immunocompromised patients.