Cowden syndrome (CS): is an autosomal dominant disorder characterized by the formation of multiple malformations involving all organs originating from 3 germ layers. The classical malformation tumor that combines with Cowden syndrome is the hair sheath tumor. Affected family members are at high risk of developing breast cancer and non-myeloid thyroid cancer. The syndrome is caused by mutations in the PTEN/MMAC1 gene. Symptoms and signs: The syndrome occurs in adults aged 20 to 40 years with a triad of multiple facial nodules, oral mucosal fibromas, and distal limb punctate keratosis. Facial nodules are common warts, mostly clustered around the mouth, nose and ears, and appear flesh-colored, pink or tan. Oral lesions are keratinized or smooth cobblestone-like papules, papillomas on the lips and furrowed tongue. There are multiple, small hyperkeratotic papillomas on the extremities. In addition, the disease can be associated with a variety of systemic diseases and tumors, including fibrocystic disease, thyroid adenomas and carcinomas, goiter, colonic adenomas, polyps and diverticula, gastric polyps, uterine fibroids, and skeletal system abnormalities. Breast cancer can occur in 50% of women years after the lesions occur. Pathophysiology: Most facial lesions have a histologic appearance similar to that of a solitary ectodermal root sheath tumor. Oral lesions appear as small fibromatous nodules consisting of fibers arranged in a gyrus pattern with little cellular component, or consisting of fibrovascular tissue and thickened spine layers. Lesions outside the face resemble common warts or verrucous acanthosis, with occasional mild follicular hyperplasia. Treatment: The management of multiple hair sheath tumors in Cowden’s disease itself is not important; the key is to detect visceral tumors, especially breast cancer, by examination and early management. Skin damage can be treated with retinoic acid (isotretinoin).