Background Pseudoxanthoma elasticum (PXE) is a monogenetic disease with progressive calcification of arteries and potential risk of stroke. To gain insights in the cerebral involvement in PXE, we evaluated prevalence and determinants of cerebral disease in our PXE cohort and performed a systematic review of literature. Methods Systematic history taking concerning cerebral disorders was performed in our PXE cohort. Cardiovascular risk factors were compared between PXE patients with and without cerebral disease. Additionally, Pubmed, Embase, the Cochrane Library and PsycINFO were systematically reviewed for studies published up to August 2016 about cerebral disease in PXE. Results Of the 178 PXE patients 31 (17%) had cerebral disease including ischemic stroke (n = 15, 8%) or transient ischemic attack (n = 13, 7%). The cerebral disease group was older (61 ± 12 vs. 52 ± 15 years, adjusted p = 0.004) and had less favorable profiles of traditional cardiovascular risk factors regarding the use of lipid lowering medication (61% vs. 31%, adjusted p = 0.037) and levels of HDL-cholesterol (1.4 ± 0.3 vs. 1.6 ± 0.4 mmol/L, adjusted p = 0.005). One prospective cohort study reporting an incidence rate of ischemic stroke of 477/100,000/year and two cross-sectional studies with a reported prevalence of ischemic stroke of 14% and 0% were identified. Furthermore, 53 unique cases of cerebral disease in PXE including ischemic stroke (n = 16) and transient ischemic attack (n = 7) were reported. Conclusions Physicians and patients should be aware of the prevalent occurrence of cerebrovascular disease in PXE, which further stresses the importance of strict cardiovascular risk management in these patients.