Chromosome-specific DNA small tandem repeats (STRs), amplified by quantitative fluorescent polymerase chain reactions, have been successfully employed for the rapid prenatal detection of human major numeric aneuploidies. These assays – which can be performed in a few hours – can be used either as preliminary investigations aimed at relieving the anxiety of parents waiting for the results of conventional cytogenetic analysis or as prenatal diagnostic tests on samples retrieved from mothers at high risk of having an affected fetus according to previous biochemical or ultrasound tests. Here we discuss the possibility of performing prenatal diagnosis with this method as the only approach to detect numerical disorders affecting chromosomes 21,18,13,X and Y in populations where the use of conventional cytogenetic tests is hampered by technical and economical difficulties. The advantages of the quantitative fluorescent tests are that they are accurate, relatively economic and that a single operator can perform up to 40–50 prenatal diagnoses per day. Furthermore, chromosome-specific STRs, as well as primers for the detection of single gene defects, can be included in a multiplex assay. The tests can be carried out also on a very small number of amniotic or chorionic cells.