The relation between APOE genotypes with cerebral microbleeds (CMBs) was investigated on the basis of the location of CMBs in 569 patients with ischemic stroke. With respect to the ?2 or ?4 allele carrier, the adjusted odds ratio was 1.87 (1.06 to 3.28) for lobar CMBs but 1.21 (0.82 to 1.87) for nonlobar CMBs. These analyses revealed that the ?2 allele may contribute to the genesis of lobar CMBs to a greater extent than the ?4 allele, instead of nonlobar CMBs. These results suggest that the pathogenesis of CMBs may differ depending on not only the frequency and distribution of CMBs but also their association with the APOE genotypes.