Coincidence of pulmonal sarcoidosis and progressive multifocal leukoencephalopathy (PML) rarely occurs. So far an entire course has been recorded in only very few cases. We demonstrate the case of a 49-year-old male developing an infratentorial localized PML in the setting of advanced pulmonal sarcoidosis. PML was not included in the diagnostic considerations in the first instance. Regarding the diagnosis of pulmonal sarcoidosis proved by lung biopsy, the neurological impairment was first thought to be due to a neurosarcoidosis. But magnetic resonance tomography (MRI) clearly showed a demyelination process in the cerebellum. Because of the inconsistency of the radiological findings with a neurosarcoidosis the diagnosis of an acute disseminated encephalomyelitis (ADEM) was favoured. Therefore, the patient was initially treated with corticosteroids. Because of increasing deterioration further diagnostic testings were performed. In the cerebrospinal fluid (CSF) as well as in the paraffin-embedded tissue of a stereotactical brain biopsy JCV-DNA was successfully demonstrated by PCR. Cidofovir was administered. The progression of the disease could not be influenced. The patient died 5 months after the first neurological symptoms. This report stresses the diagnostic difficulties considering patients with sarcoidosis and neurological symptoms.