Underlying pathologies of stroke of unknown cause include atherosclerosis in brain arteries, either intracranial (e.g. moderate middle cerebral artery stenosis), extracranial (e.g. vertebral artery origin stenosis) or proximal (e.g. thick plaques in the aortic arch), thought to be unrelated to the stroke; cardiac findings of undetermined causal link (e.g. patent foramen ovale); incomplete or late workup responsible for true, undiagnosed cause (e.g. arterial dissection, mobile intracardiac/luminal thrombus disappeared at the time of examination). In the next years, new diagnostic tools may hopefully determine which of these pathologies are or are not causally related to stroke. Copyright (C) 2009 S. Karger AG, Basel