BACKGROUND: Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by immunodeficiency, thrombocytopenia, and atopic dermatitis. OBSERVATIONS: This infant presented at birth with petechiae and bruising, with severe neonatal thrombocytopenia. Genetic testing for WAS revealed a variant of unknown significance hemizygous missense mutation in the WAS gene. This variant has not previously been reported. On the basis of the patient's clinical course including bleeding, infection, abnormal immune evaluation, and dermatologic sequelae, he was diagnosed with WAS and underwent allogeneic hematopoietic stem cell transplantation. CONCLUSIONS: We report a novel mutation in the WAS gene that causes a phenotypic presentation of Wiskott-Aldrich Syndrome.