In 2004, the UK National Screening Committee suggested that rapid screening tests, such as fluorescence in-situ hybridization (FISH) and/or quantitative fluorescence PCR (QF-PCR), should replace prenatal diagnosis of Down syndrome performed by conventional karyotyping. However, doubts have been expressed that replacement of conventional cytogenetic investigations would result in a substantial number of infants affected by preventable handicaps. Based on a brief analysis of 28,000 prenatal tests performed in genetic units, this paper discusses the advantages of using QF-PCR. All normal fetuses were correctly diagnosed without false positive results and approximately 93% major chromosome disorders were detected by the molecular approach. The need for cytogenetic tests was thus greatly reduced, since pregnancy can be terminated, if necessary, without the need to confirm the results. A careful combination of accurately performed non-invasive ultrasound and maternal blood tests, eventually followed by QF-PCR, should reduce the need for conventional chromosome analyses.