Homozygous familial hypercholesterolemia (HFHC) is a rare inherited condition with an incidence of 1 in a million. It is associated with severe premature atherosclerosis and early death from cardiovascular complication. Mutation in the gene that encodes the synthesis of the cellular receptor for low density lipoprotein (LDL) is responsible for this metabolic disorder. Currently, the only effective treatment for this disease is liver transplantation, which alone or in association with medications, normalizes plasma cholesterol level. The authors report the results of liver transplantation for 2 cases of HFHC in Shiraz transplant unit, Shiraz, Iran. First case, a 15 y/o boy, received whole liver from a deceased donor and the second an 11 y/o boy who received left lobe from a living donor (his mother). The older boy had severe atherosclerotic heart disease and undergone coronary artery bypass grafting 5 months before transplantation. Both had preoperative plasma cholesterol level higher than 750 mg/dl which didn’t respond to medical therapy. Thyroid and liver function tests were normal. After the operation the patients received methylprednisolone as a pulse therapy followed by oral prednisolone, mycophenolate mofetil and tacrolimus for immunosuppression. Their hospital stay was 24 and 13 days respectively. The lipid concentration returned rapidly to normal range in the 1st week after operation and remained in this range in the first 6 moths of follow-up. In conclusion, liver transplantation offers highly effective treatment for HFHC. It's better to operate the patients before severe atherosclerotic changes in the coronary arteries. All patients must be undergone complete cardiac evaluation before the surgery.