Segmental duplications are large genomic segments of recent origin and nearly identical sequence. Segmental duplications account for up to 5% of the human genome and they are often involved in genomic rearrangements and human disease. We developed a rapid computational method to characterize segmental duplications in the mouse and the human genomes according to four sequence assemblies for each species. Segmental duplication content in the mouse genome assemblies has largely changed over the four releases (from 0.2 to 1.2%, 4.5 and 3.0%), while in the four human assemblies duplication content was 4.8, 3.5, 3.7 and 3.7%, respectively. This suggests that cataloguing and assembling duplications has been challenging in both genomes and any interpretation of comparative analyses of duplication content must keep this in perspective to avoid artifacts. Human and mouse segmental duplications are more frequent than expected in regions where there is a syntenic discontinuity and the duplication content in syntenic regions decreases significantly with distance from breakpoints of synteny. These observations indicate that in mouse and human the frequency of segmental duplications is strongly correlated with distance to human and mouse syntenic breaks or the most dynamic regions in evolution..