A case of combined pentalogy of Cantrell with sirenomelia in a monozygotic twin is described. Similar cases from the world literature are reviewed. Current concepts on the etiology of anterior midline ventral wall defects and sirenomelia are detailed. It has been proposed that anterior midline ventral wall defects may be caused by either monozygotic twinning or vascular dysplasia. Likewise, a vascular steal phenomenon causes sirenomelia. A common etiology for these defects, an alteration in vascular development, is proposed.