Vitiligo is the most common depigmenting skin disorder with an estimated prevalence of 0.5–2% of the population in both adults and children worldwide. Death receptor 3 is a typical member of TNFRSF which play a role in apoptotic signalling and differentiation. DR3 is considered the primary activating receptor of TL1A and is predominantly expressed on leucocytes. DR3 expression is significantly upregulated on various activated cells in the immune system, including T lymphocytes, B lymphocytes, natural killer T (NKT) cells, dendritic cells and macrophages. The aim of this study was to study the expression of death receptor 3 (DR3) on CD4 positive lymphocytes on patients with vitiligo . This study was a case control study that included 50 patients with vitiligo in addition to 25 apparently healthy individuals of matched age and sex as a control group. All patients were recruited from the outpatient clinic of Dermatology, Venereology and Andrology Department of Benha University Hospitals. DR3 showed fair AUC (AUC=0.794). At cut off value of 23.8, sensitivity was72%, specificity was 80%, PPV was 87.8%, NPV was 58.8%, and accuracy was 74.7%. DR3 expression level was significantly higher in vitiligo cases when compared to control group. DR3 expression level was significantly correlated with BSA %. DR3 expression level was suggested to be independent predictor of vitiligo susceptibility and Extent.