This paper reports the identification of thousands of extrachromosomal circular DNA molecules in mouse tissues and in mouse and human cell lines. These small 200–400 bp 'microDNAs' map to unique sequences in the genome; these are mostly located in the 5′ untranslated region of genes and in exons and CpG islands. Chromosomal microdeletions due to the excision and loss of microDNAs lead to a considerable degree of mosaicism in the mouse brain and possibly also to the frequent germline mosaicism reported in humans by the 1000 Genomes Project.