Harlequin ichthyosis (HI) is the most severe skin disease of the autosomal recessive congenital ichthyosis, showing typical clinical appearance of generalized, thick, yellowish, hyperkeratotic plates with deep erythematous fissures, with a high risk of dehydration, electrolyte imbalance and skin infection resulting in a high mortality rate up to 50% in the newborn. Here, we present a newborn girl with HI which was genetically confirmed by whole exome sequencing and quantitative PCR analysis. A female girl was born via vaginal delivery at 35+4 weeks of gestation without other perinatal risks except for prenatally suspected club foot and hands. At the delivery room, whole body skin except for lips was covered with a white opaque membrane with erosion. Both hands and feet were encapsulated in membrane that looked like white bulla. She was cared in an incubator with humidity set at 70% to prevent excessive water loss through skin. Enteral feeding via nasogastric tube in conjunction with total parental nutrition was started because of poor oral sucking, and electrolyte imbalance was not observed. Empirical antibiotics therapy was started to avoid skin infection and neonatal sepsis. Oral retinoic acid was started and vaseline was applied to whole body skin for managing congenital ichthyosis. On the 4th day of age, right toe was turned into dark brown because of reduced blood circulation due to ichthyosis membrane contraction, therefore capsulotomy was performed. The ichthyosis covering whole body slowly peeled off by about 14 days after birth, about 20 % of membranes was remained and a thin scaling was formed. She discharged at 27 days of birth with keeping vaseline application on the skin. Whole exome sequencing and quantitative PCR analysis identified compound heterozygous mutations of the ABCA12 gene and HI was confirmed; p.N1380S from the mother and a partial deletion including exon 9 from the father. Now, she is 5 months old showing normal developmental milestones.