Objective: To compare karyotypic, ultrasonographic, and prognostic features of septated cystic hygromas and nonseptated cystic hygromas in second-trimester fetuses. Methods: A computerized ultrasound data base was used to identify fetuses diagnosed with cystic hygromas at 14-22 weeks' gestation. Photographs from the initial ultrasound were reviewed retrospectively for hygroma type (septated or nonseptated) and any abnormal structural findings. Fetal karyotypes were obtained from amniotic fluid, aspiration of hygroma pouches, or fetal tissue culture. Pregnancy outcome information was obtained from hospital charts and physician office records. Ultrasound findings were then compared with fetal karyotype results and pregnancy outcome data. Results: From 1990 to 1995, 61 fetuses with cystic hygromas were identified. Karyotypes were obtained in 55 fetuses, and pregnancy outcome was available for 59. Abnormal karyotype was present in 42 of 55 fetuses (76%). The most common chromosomal abnormality in septated hygromas was the 45,X karyotype. Trisomy 21 was the most common chromosomal abnormality in nonseptated hygromas. Compared with fetuses with nonseptated cystic hygromas, those with septated cystic hygromas were more likely to be aneuploid (33 of 39 [85%] versus nine of 16 [56%]; P = .03), more likely to develop hydrops (27 of 45 [60%] versus three of 16 [19%]; P = .005), and less likely to be live-born (one of 44 [2%] versus four of 15 [27%]; P = .01). Conclusions: Fetuses with septated cystic hygromas are more likely to be aneuploid and to develop hydrops, and thus are less likely to survive than fetuses with nonseptated hygromas.