Abstract: We report four cases of diffuse infantile hepatic hemangioma, a rare but potentially life-threatening subset of hepatic hemangiomas. All patients demonstrated distinctive dome-shaped red–purple cutaneous hemangiomas. Two patients responded to steroids and propranolol (one in combination with vincristine), and two responded to steroids and vincristine. After a systematic literature review, we identified 26 previously reported cases of diffuse infantile hepatic hemangioma. Diffuse infantile hepatic hemangioma had a mortality rate of 17% and a >70% incidence of hypothyroidism, often severe (n = 30). More than one-third of patients developed heart failure (high output in half the cases). Based on our experience, early aggressive medical management, as well as thyroid replacement when indicated, should be initiated early in the course of diffuse infantile hepatic hemangioma pending evaluation for liver transplant.