Prenatal diagnosis of monoamnionicity is necessary for optimal care of a twin gestation. When the fetuses are discordant for a lethal anomaly, unequivocal confirmation is imperative. Ultrasound evaluation of our patient revealed a twin gestation discordant for anencephaly and with possible monoamnionicity. When sonography was inconclusive, CT amniography confirmed a single amniotic cavity, permitting appropriate parental counseling and pregnancy management. CT amniography is a useful adjunct to ultrasound in evaluating twins discordant for a lethal anomaly when monoamnionicity is suspected.