Vitiligo is an autoimmune polygenic disorder, characterized by loss of pigmentation due to melanocyte destruction. Multiple genes and environmental triggers are thought to play a role in inducing vitiligo. Etiological hypothesis suggested for etiopathogenesis of vitiligo include gender, immunological, neuro-hormonal and other environmental factors. Genes possibly play a role in all aspects of pathogenesis of vitiligo. Most genes associated with vitiligo are involved in immune regulation and immune targeting of melanocytes. These genes and environmental factors differ across different population. Vitiligo is the most common depigmenting disorder, with a prevalence of approximately (0.5-2%) in the world population. CD44 gene has been linked with the development of several autoimmune disorders. CD44 is encoded by single gene, located on chromosome 11p13. CD44 is a cell surface glycoprotein with various functions, and is involved in a number of biological processes including lymphocyte migration, extravasations, homing, activation, and apoptosis, especially those involving a role in T-cell development. The purpose of the present work was to investigate the association between an inherited genetic polymorphism at CD44 gene and vitiligo in Egyptian patients. The present study included 50 vitiligo patients and 49 apparently healthy age and sex matched subjects as control group. Patients were recruited from the outpatient clinic of Dermatology and Andrology Department Benha university hospitals. All studied individuals were subjected to complete history taking and complete clinical examination. Patients were classified into three types (vitiligo vulgaris, acrofacial and universalis) and disease extent was assessed by body surface area (BSA) score. This study included 2 groups; patients group included 50 patients with vitiligo, 15 males (30%) and 35 females (70%), and control group included 49 healthy, age and sex matched individuals. This sample of individuals was selected randomly from population in Qalyubia Governate. Results of the present study showed a statistically insignificant difference between vitiligo patients and control groups regarding the frequency of CD44 genotypes and alleles.