Acromegaly, when left untreated, is associated with premature mortality which is chiefly related to cardiovascular complications. We report on a 50-year-old acromegalic woman, resistant to therapy, who died suddenly because of thoracic aortic rupture and massive bleeding into the left pleural space. The postmortem examination disclosed, nearby the point of rupture, a pulmonary abscess as well as extensive intrinsic alteration of arteries originating from the aortic arch and aorta itself, which featured microscopic cystic medial necrosis. We discussed how these aspects could be related to long-term exposition to growth hormone excess. In particular, this case gives further evidence of vascular system frailty in acromegaly.