A preterm newborn affected by congenital syphilis, born to mother not treated during pregnancy is described. The clinical picture was characterized by respiratory distress, cutaneous manifestations, massive hepatosplenomegaly, severe anemia, thrombocytopenia, disseminated intravascular coagulation syndrome and hypoalbuminemia. The patient was treated with daily injections of 190,500 units of crystalline penicillin G for 14 days. Premature infants with these symptoms and signs should be evaluated for congenital syphilis.