Marfan syndrome (MFS) is a heritable disorder of the connective tissue which has been linked to mutations in the FBN (fibrillin-1) gene. Murine knockouts of the FBN gene show increased interstitial fibrosis and TGF-beta (tumor growth factor-beta) gene activation. Abnormal TGF-beta expression has previously been linked to radiation-induced fibrosis, suggesting a possible link between MFS and increased late effects following radiotherapy. Herein we report two cases in which MFS patients treated with radical radiotherapy without undue acute or late radiotherapy toxicity suggesting that radiotherapy should not be withheld from MFS patients. MFS patients may provide a unique clinico-translational setting to test associations between FBN mutations, TGF-beta activation and the risk of tissue fibrosis.