Holoprosencephaly is a congenital anomaly of the central nervous system whose prenatal sonographic appearance may to similar to that of ventriculomegaly. A clear differential diagnosis is extremely important because the two conditions have different prognoses and therefore require different obstetric management. Eight cases of prenatally recognized holoprosencephaly are analyzed and criteria for a specific diagnosis proposed. The specificity and limitations of ultrasound findings, such as identification of a holoventricle, presence of a dorsal sac, and facial anomalies are discussed.