OBJECTIVE: QF-PCR is an inexpensive and reliable method for aneuploidy screening; however, despite its obvious advantages, it is not in routine use in the United States. Our objective in the present study was to validate QF-PCR as a means for prenatal aneuploidy screening in our institution. METHODS: A QF-PCR assay using 15 primer pairs located on chromosomes 13, 18, 21 X and Y was established for aneuploidy screening. Amniotic fluid (AF) and chorionic villus sampling (CVS) samples consisting only of the cells recovered from the plasticware discarded by our institutional cytogenetics laboratory were collected and DNA was prepared by a simple and inexpensive microwave procedure. QF-PCR was then performed and interpreted using established criteria. RESULTS: 687 consecutive prenatal samples were screened in a blinded prospective manner, and results were compared to those obtained by conventional cytogenetics. 100% of autosomal trisomies were detected, and there were zero false positives. A single case each of XXY and 45X were missed. CONCLUSIONS: QF-PCR for prenatal aneuploidy screening was validated in our laboratory and has now been approved by the New York State Clinical Laboratory Evaluation Program. We propose a simple protocol for integrating QF-PCR into the normal cytogenetics laboratory workflow.