Harlequin ichthyosis is the most severe form of keratinizing disorders. Neonates usually die within the first days of life from infections and dehydration-related complications. Prenatal diagnosis remains difficult but may be possible in high risk pregnancies by performing a fetal skin biopsy or by three-dimensional ultrasonography. Ultrasound of a 27-year-old woman, gravida 1, revealed a 28-week fetus with oligohydramnios without obvious deform-ity. At 36 weeks of gestation, a male infant weighing 2450 g was delivered with cesarean section. APGAR scores were 6, 7 and 8 at 1, 5, and 10 minutes respectively. Parchment-like appearance of the skin, ectropion, eclabium, and low-set dysplastic ears characteristic of Harlequin ichthyosis were identified. Despite optimum treatment with cathecholamines, antibiotics and ventilatory support, he died due to sepsis on the fifth day. In this report we discussed the recent developments in the diagnosis and treatment of Harlequin ichtiyosis.