Genetic counseling in cases of multiple pregnancies shows marked differences compared to singleton pregnancies. The rising rate of multiple pregnancies and its association with advanced maternal age has expanded the need for prenatal diagnosis in twins and higher-order gestations. However, the request for invasive prenatal diagnostic procedures often differs in multiple and singleton pregnancies. This is in particular true when the multiple pregnancy occurred after assisted reproductive technology. In case of twin pregnancies, the distinction between a mono- and dizygotic pregnancy may facilitate the decision about obtaining a single or two samples. Discordant anomalies pose a special problem. Discordant anomalies are in rare instances even observed in monozygotic pregnancies. Here, we summarize the clinical, analysis-related and ethical problems regarding genetic counseling in multiple pregnancies.