AbstractThe aim of this study was to quantify the maternal age‐specific risk for trisomy 21 mosaicism. Data were obtained on 322 trisomy 21 diagnoses with mosaicism and 27,943 simple trisomy 21 diagnoses recorded in the National Down Syndrome Cytogenetic Register from 1989 to 2009 in England and Wales. Trisomy 21 cases with mosaicism have a mean maternal age of 33.1 years compared to 35.0 years for free trisomy 21 cases. Sixty‐seven percent of trisomy 21 diagnoses with mosaicism are maternal age dependent, with a risk 0.8% that of the corresponding maternal age specific risk for simple trisomy 21. However 33% (0.8 per 100,000 births) are not maternal age dependent, indicating that maternal age is not the only risk factor for mosaicism. Trisomy 21 diagnoses with mosaicism are more likely to be female than free trisomy 21 diagnoses, however there was no association of fetal sex with maternal age which indicates that there is another factor involved in the presence of mosaicism not associated with maternal age, but associated with fetal sex. © 2012 Wiley Periodicals, Inc.