Progressive multifocal leukoencephalopathy (PML) is a rare infectious cause of sub-acute neurological symptoms, and occurs predominantly in immunocompromised patients. PML is caused by reactivation of the JC virus. A 79-year-old man with a history of chronic B-cell lymphatic leukaemia (B-CLL) presented at our hospital with a neurological deficit of the left side of his body. He was initially diagnosed with a right-hemisphere stroke. Two months later he returned with progressive paresis and on an MRI of the brain we saw an increase in abnormalities of the white matter. On suspicion of PML we conducted PCR for JC virus on cerebrospinal fluid (CSF), which was negative. Histopathological investigations of a brain biopsy confirmed the diagnosis of PML, four months after he first presented. PML is a rare cause of sub-acute neurological symptoms. PML can be difficult to diagnose as a PCR of CSF for JC virus in the early stages of PML can give a false negative result. If PML is suspected, histological investigation of a brain biopsy is necessary.