In a fetal variation of circle of Willis (CoW) there is an embryological defect of the primary collateral circulation. Besides the fact that collateral flow cannot develop between anterior and posterior circulation, the tentorium namely prevents cerebellar vessels from connecting to the supra-tentorium territory. Therefore patients with a fetal variation of circle of Willis could be more prone to develop vascular insufficiency. An association between the regional cerebral blood volume (rCBV) inter-hemispheric asymmetry and CoW collateralization was observed with a topographic significance of corona radiate rather than centrum semiovale. An overview of the literature is given. We propose a fetal variation of circle of Willis as a risk factor for stroke should be subject of further investigation.