In the Netherlands, first-trimester combined testing (FCT), including the measurement of fetal nuchal translucency (NT) thickness, has been offered to all pregnant women since 2007. Since 2014, noninvasive prenatal testing (NIPT) has been offered to women with an elevated trisomy risk determined by FCT. Because high NT is associated with other anomalies and genetic syndromes beyond trisomies 13, 18, and 21, NIPT is not offered when NT is 3.5 mm or greater. As NIPT becomes less expansive and more widely available, it may replace FCT. This study examines the question as to whether NIPT should replace FCT, how many pregnancies with fetal chromosomal anomalies other than trisomies 13, 18, and 21 and with NT of 3.5 mm or greater would remain undetected. This retrospective cohort study used data from the Department of Obstetrics of the University Medical Center Utrecht, including all fetuses referred because of an NT of 3.5 mm or greater between January 2008 and January 2013. All pregnancies had NT measurements, and risks for trisomies 13, 18, and 21 were calculated. Patients offered amniocentesis or chorionic villus sampling and second-trimester ultrasound if they had NT of 3.5 mm or greater. Outcome for pregnancy included born alive–normal outcome, born alive–abnormal outcome, termination of pregnancy, or fetal demise. Of 25,057 NT measurements obtained on singleton pregnancies during the study period, 225 (0.9%) had an NT of 3.5 mm or greater. Of those, prenatal array analysis and/or karyotyping were performed in 221 (93.8%). A chromosomal anomaly was identified in 103 (48.8%) of the 225 fetuses/newborns, and in 79 (77.7%), the anomaly was trisomy 13, 18, or 21. Of the remaining 24 pregnancies, 11 resulted in fetal demise, 10 had detection of fetal ultrasound anomalies, and 3 had a chromosomal anomaly, but normal ultrasound findings and no fetal demise. Of those, 1 anomaly was a 47,XXX karyotype, 1 had 2 de novo deletions, and 1 had a paternal deletion causing Prader-Willi syndrome. In the cohort of 25,057 pregnancies, a protocol of NIPT rather than NT measurement and a second-trimester ultrasound would have missed a chromosomal anomaly in only 0.01%. If NIPT is offered to all pregnant women, the value of NT measurement in detecting fetal chromosomal anomalies would be small.