Technological advances in prenatal diagnostic ultrasound have led to identifying defects of the midline structures of the head whose etiology is still largely unknown although mostly related to underdiagnosed genetic syndromes. We describe three cases of solitary median maxillary central incisor syndrome in which two-dimensional second trimester of pregnancy sonography showed the characteristic dental feature of a solitary central incisor in the maxilla. This syndrome is a complex condition that may appear isolated or in association with other midline developmental anomalies within the broad holoprosencephaly spectrum. Early recognition of the syndrome is of great importance for establishing the diagnosis, performing additional investigation, and management of associated anomalies.