Second-trimester 2D ultrasound (US) assessment of the fetal anatomy, as proposed by worldwide guidelines, allows detecting the majority of fetal malformation. However, the detection rates of fetal facial anomalies seem to still be low, mostly in cases of isolated facial malformation. The purpose of this research was to assess and analyze the concordance between the antenatal imaging findings from second-trimester US screening and the results of fetal postmortem autopsy. Between January 2010 and January 2020, there were 43 cases where fetuses with prenatal ultrasound diagnosis of a face abnormality, associated or not with a genetic syndrome or chromosomal disorder, following intrauterine death (IUD) or termination of pregnancy (TOP) after the 13 weeks of pregnancy, underwent autopsy in the Pathological Anatomy section of Bari Polyclinic specializing in feto-placental autopsies. The diagnosis of the fetal facial defects at ultrasound was compared with the findings at autopsy in all cases. A very high level of agreement between prenatal ultrasound and autopsy findings was found for facial abnormalities associated with genetic syndromes or numerical abnormality of chromosomes. A lower level of concordance was instead found in isolated facial defects or those associated with other organ anomalies, but not associated with genetic syndrome or numerical chromosome anomaly. A detailed examination of aborted fetuses led to successful quality control of early-second-trimester ultrasound detection of facial anomalies; however, it was less accurate for the isolated ones. It is, thus, reasonable to propose a systematic early-second-trimester prenatal ultrasound screening for facial anatomy by operators specialized in fetal medicine field, using 2D, 3D, and 4D techniques (two-, three-, and four-dimensional ultrasound).