BACKGROUND Hereditary hemorrhagic telangiectasia, also known as Osler-Weber-Rendu disease, induces arteriovenous malformations in visceral organs. Arteriovenous malformations increase the risk of severe infections and are a common complication associated with hemorrhagic telangiectasia. However, cases of endocarditis associated with hemorrhagic telangiectasia are rarely reported. Although hemorrhagic telangiectasia causes erythematous macules on the extremities, these macules are usually painless. We encountered a rare case of infective endocarditis in a patient with Osler-Weber-Rendu disease. METHODS A 52-year-old Japanese woman who was diagnosed with hemorrhagic telangiectasia 5 years prior presented to our hospital with fever and muscular pain. She had erythematous nodules and tenderness on the finger, heel, and toe, suggestive of Osler's nodes. A physical examination revealed tachycardia with a 3/6 pansystolic murmur. A transesophageal echocardiogram showed vegetations along the atrial side of the mitral valve and mild mitral regurgitation because of prolapse of the anterior commissure. Methicillin-sensitive Staphylococcus aureus was identified in the blood cultures. Detection of distinctive skin lesions, so-called Osler's nodes, was the symptomatic key to early diagnosis, and the patient was treated without surgery. She was discharged with negative blood cultures after a 6-week intravenous antibiotic administration. CONCLUSIONS Our report highlights the importance of considering the risk of extracerebral infections including endocarditis in hemorrhagic telangiectasia. This rare case effectively demonstrates the importance of proper diagnosis of skin lesions.