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Three fetuses with agnathia‐otocephaly complex representing different degrees of embryonic maldevelopment are reported. The study of the three cases and of the anterior embryonic disc supports the concept that an altered embryologic development might have taken place at Carnegie stages 10 (embryonic days 22 or 23) and 11 (embryonic days 23–26). Karyotypic abnormalities and aberrant gene expression of sonic hedgehog and paired‐related homeobox genes are discussed as the cytogenetic and molecular basis of agnathia‐otocephaly complex. © 2002 Wiley‐Liss, Inc.