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The immunohistochemical application of CD3 (T lymphocytes) and CD20 (B lymphocytes) markers in duodenal biopsy can facilitate the detection of the number and distribution of intraepithelial lymphocytes along the villi, which is regarded as a key factor for accurate diagnosis of celiac disease. This study aims at finding a relationship between CD3 and CD20 immunohistochemical and histopathological alterations of celiac disease, and at investigating whether the application of those immunohistochemical stainings would improve the detection of lymphocytosis within the epithelium and add advantages to celiac disease diagnosis.Biopsies were obtained from 100 individuals and stained with hematoxylin and eosin (HE). They were then evaluated according to the Marsh classification. After that, staining for CD3 and CD20 was individually done and assessed.The overall mean intraepithelial lymphocyte count per 100 enterocytes for HE was 23.1 (95% confidence interval [CI] = 19.52-26.68), and for immunohistochemistry by CD3 and CD20 was 27.84 (95% CI = 24.31-31.38). The difference was highly significant