ABSTRACT: Structural copy number variation (CNV) is a frequent cause of human variation and disease. Evidence is mounting that somatic acquired CNVs are prevalent, with mosaicisms of large segmental CNVs in blood found in up to one percent of both the healthy and patient populations. It is generally accepted that such constitutional mosaicisms are derived from postzygotic somatic mutations. However, few studies have tested this assumption. Here we determined the origin of CNVs which coexist with a normal cell line in nine individuals. We show that in 2/9 the CNV originated during meiosis. The existence of two cell lines with 46 chromosomes thus resulted from two parallel trisomy rescue events during postzygotic mitoses.