The critical need for rapid and reliable karyotype analysis can be no greater than in the setting of sonographic fetal anomalies. Fluorescent in situ hybridization (FISH) directly applied to interphase chromosomes can decrease the time required to identify the common aneuploidies. Our retrospective study reviewed 50 consecutive patients with sonographic fetal anomalies who underwent FISH. Within this high risk group, nonmosaic chromosomal aneuploidies were present in 16% of the fetuses (8 of 50), and 2 additional fetuses had cytogenetic abnormalities: 1 case, 46, XY,-12,+der(12)t(12;13)(p13; q14.1), and 1 case a 10% mosaic for trisomy 21. Of the 10 cytogenetically abnormal fetuses, FISH was able to identify correctly all 8 of the nonmosaic aneuploidies within 2 days of receipt of the specimen in the laboratory. Clinical decisions can be made on the basis of concordant FISH and ultrasound abnormalities, shortening the decision-making process for most of the aneuploid cases. However, our experience demonstrates some of the limitations of current FISH protocols and the continued necessity for formal karyotype analysis.