The detection of marker chromosomes at prenatal diagnosis raises serious concerns regarding the phenotypic consequences on the fetus. Traditionally the classical approach to the problem relied upon the cytogenetic analysis of the marker chromosome by different banding techniques to ascertain its euchromatic content. This indirect methodology doesn't allow to trace the origin of the marker and to properly narrow the molecular boundaries of the euchromatic region. FISH technology by means of DNA probes regionally localized is a powerful tool to address these issues, allowing to determine the exact origin of the markers and more refined criteria for studying karyotype-phenotype correlations. This facilitates genetic counseling and the decision making for the parents. Here we describe our experience of integrated approach (molecular and classical cytogenetics) in two de novo cases of marker chromosomes (iso 18p and inv dup 15), detected at amniocentesis.