The role of histopathology for diagnosing celiac disease (CD) has been recently challenged. However, based in our experience with roughly 4,600 distal duodenal and jejunal biopsies in children it is apparent that appropriate biopsy site, handling, processing, and microscopic evaluation result in a consistent pattern of microscopic changes which allows strong clinical-pathologic correlation. A simple way for establishing the villous/crypt (V/C) ratio is proposed. Normal mucosa displays a V/C ratio of 2.5 or more. Villous atrophy is then graded according to the V/C ratio as follows: Grade 1: 2.5-2; Grade 2: 1-2; Grade 3: 1-0.5, and Grade 4: less than 0.5. The grading should be done in areas of the biopsy where at least 2 to 3 crypts are present in almost its full length. CD disease was consistently associated with villous atrophy grades 3 and 4, which fully recovered or maintained Grade 1 after gluten-free diet. Grade 2 biopsies were rare and related to incomplete gluten-free diet. Patchy lesions were never seen as were patients with normal biopsies later developing mucosal atrophy. Histopathologic evaluation of mucosal biopsies to rule out CD requires adequate biopsy site (distal duodenum or proximal jejunum), and proper handling (oriented material), processing (cutting on edge) and interpretation. The proposed villous atrophy grading may help to adequately compare experiences from different centers as well as to reconcile apparent different findings in separate biopsies. In children histopathology keeps on having a central role for CD diagnosis.