The biological function and evolution of microRNAs (miRNAs), an important class of noncoding regulatory genes, have attracted wide interest. However, their evolutionary impact on gene order rearrangements remains unknown. We examined the gene-order stability of miRNA-neighboring regions by a comparative human-mouse genomic analysis and found that the neighboring genes of human miRNAs tend to have a conserved gene order. This observation cannot be attributed to the functional bias of neighboring genes, and is a unique characteristic of miRNAs but not other noncoding RNAs. Our findings suggest that mammalian miRNAs stabilize the genomic architecture in evolution.