Abstract: Darier-White Disease is a genetic disorder that involved the keratinized and non-keratinized epithelium of mucous membrane, cornea and submandibular glands. It is manifested in summer and predisposed by warm and wet weather conditions. The complications of disease are aggravated by bacterial and herpes simplex virus infections. Diagnosis is based on positive family history, clinical and histopathological characteristics of the disease. Although, surgical treatment is useful for hypertrophic kinds of the disease, systemic Isotretinoin is a choice treatment. We herein present two patients with Darier-White Disease. Case one was a 30 year-old man with desquamative papules for 15 years. The surface of lesions was greasy and rough. The lesions were on face, auxiliary and upper chest area. The diagnosis was done after biopsy from forehead lesions. Case two was a 22 year old man with positive history of lesions on hands from childhood. The spreading papules were appeared in neck area during recent year. Patient referred with lesions on hands, wrist, posterior side of elbow, scapulae, neck and anterior and posterior of the trunk. The diagnosis was confirmed after biopsy from abdominal surface lesions. There is no cutaneous malignancies report related to Darier`s disease in prior studies. Although, Basal Cell Carcinoma (BCC) and a rare kind of sweet gland`s tumor were reported, squamous cell carcinoma in digestive system and skin and hyperkeratosis in foot nail was reported in heterozygote mice. Differentiation between human and mice is needed future studies.