Two unrelated patients with clinical characteristics of both Lhermitte-Duclos disease and the autosomal dominant Cowden disease are reported from the Department of Neurology, University Hospital, Leiden, The Netherlands. Patient 1 was a mentally retarded woman with a large head, a high arched palate, dysarthria, mild cerebellar signs, and a single seizure at the age of 37 years. She also exhibited multiple papules on her nose, cheek, forehead and ears and on the oral mucosa. CT scan showed a nonenhancing mass in the cerebellar vermis and left cerebellar hemisphere, enlarged third and lateral ventricles, and a hypodense lesion in the centrum semiovale of the left cerebral hemisphere. A dysplastic gangliocytoma of the left cerebellar hemisphere was diagnosed at surgical resection of the tumor. Microscopic examination of skin biopsies showed trichilemmomas. Bilateral nonmalignant breast tumors were diagnosed at follow-up. The second patient had a history of tonic-clonic seizures in childhood, thyroid surgery at age 38 and he presented with cerebellar signs at 48 years of age. A dysplastic gangliocytoma was removed from the left cerebellar hemisphere. Skin lesions included papules on the face, limbs, and on the gingiva and tongue. Siblings of both patients showed the mucocutaneous lesions, thyroid disease, breast tumors, ovarian tumors, and also neurological signs including macrocephaly, mental retardation, seizures, tremor, and dysdiadochokinesia. The authors propose that Lhermitte-Duclos disease and Cowden disease are manifestations of a single phakomatosis. [1]