The paper reports the case of a term newborn from consanguineous parents with diffuse hyperkeratotic plaques, ectropion, eclabium and auricular malformations. He was diagnosed with Harlequin ichthyosis, a rare autosomal recessive disorder caused by ABCA12 mutations. The infant received acitretin, antibiotics and escharotomies, with favourable outcome. The case highlights the importance of early and multidisciplinary management in this severe condition.