Multiple hamartoma syndrome, also known as Cowden's disease, is a rare genodermatosis with characteristic mucocutaneous lesions associated with multiple internal abnormalities. We describe a patient having classic dermatologic manifestations of Cowden's disease and multiple neoplasia including follicular adenocarcinoma of the thyroid gland with lung metastasis, intraductal breast carcinoma within a fibroadenoma, and an osteosarcoma. To our knowledge, this is the first reported case of an osteosarcoma in Cowden's disease.