Otocephaly, also known as agnathia-otocephaly complex or agnathia-microstomia-synotia complex, is a severe malformation characterized by distinct facial defects consisting of agnathia (absent or severely underdeveloped mandible), microstomia (small or punctiform mouth), and melotia/synotia (ventromedial displacement or fusion of the ears, respectively). The prenatal diagnosis of this condition has been typically on second or third trimester ultrasound after the detection of agnathia in association with polyhydramnios. However, the first-trimester diagnosis of this condition is being increasingly reported. Holoprosencephaly is the most frequent associated extrafacial anomaly, as otocephaly is present in about 10–16% of fetuses with holoprosencephaly. In this chapter, we review the main prenatal imaging findings, antenatal course, and perinatal outcome of this major facial congenital anomaly.