Intestinal biopsy is an integral part of diagnosing celiac disease.1 Historically, the diagnosis of celiac disease required three intestinal biopsies; an initial biopsy taken while the patient was on a regular gluten-containing diet (demonstrating villous atrophy), a second biopsy with the patient on a gluten-free diet (demonstrating improvement), and a third biopsy following a supervised gluten challenge (demonstrating deterioration).2 Fortunately, the availability of serologic tests highly specific for celiac disease reduced the clinical requirement to a single intestinal biopsy for diagnostic confirmation. Diagnostic accuracy with a single intestinal biopsy was estimated at 95%, similar to the three-biopsy protocol, resulting in the latter diagnostic approach no longer being necessary.3 The discovery of tissue transglutaminase as an auto-antigen of celiac disease in 1997 and the subsequent development of accurate and easily accessible serologic tests based on tissue transglutaminase further facilitated the diagnosis of celiac disease.4 The IgA anti-tissue transglutaminase antibody (anti-tTG IgA) test has been positioned as the serologic assay of choice for diagnosing celiac disease because of its high specificity (average > 97%) and adequate sensitivity.1 With increasing clinical experience over time using anti-tTG IgA, it became evident that higher antibody titers were associated with greater diagnostic accuracy. Therefore, since 2012, the guidelines of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) have proposed the no-biopsy diagnosis in selected children with anti-tTG IgA values greater than 10 times the upper limit of normal (together with a positive anti-endomysial antibody test in a separate blood sample).5 The no-biopsy approach in children has been validated in numerous prospective studies.6,7 However, the no-biopsy diagnosis continues to be a subject of debate in other regions of the world. For example, in the United States, no-biopsy diagnosis in children with anti-tTG IgA greater than 10 times the upper limit of normal is suggested as an alternative to biopsy in the American College of Gastroenterology (ACG) guidelines, but it is not recommended in the most recent guidelines of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN), which advise histologic confirmation with biopsy in all cases. No-biopsy diagnosis is even more controversial in adults. At present, only one recent guideline from the European Society for the Study of Coeliac disease (ESSCD) makes a conditional recommendation for no-biopsy diagnosis in adults under 45 years of age with anti-tTG IgA greater than 10 times the upper limit of normal.8 Consequently, studies on adults that report on the predictive capacity of anti-tTG IgA for detecting villous atrophy in different populations are very useful. The study by Fernández-Ramírez et al.9 describes the clinical experience at a specialized referral center in Mexico City involving 53 patients with intestinal biopsy-confirmed celiac disease (that included the histologic review by gastrointestinal pathologists). Most of the patients had a classic clinical presentation that included chronic diarrhea and/or diverse nutritional deficiencies. In such a clinical context, with high pre-test probability, the predictive capacity of anti-tTG IgA antibodies for detecting intestinal villous atrophy was evaluated. Of the 53 celiacs, 19 patients with anti-tTG IgA levels greater than 10 times the upper limit of normal had 100% positive predictive value for intestinal villous atrophy in the intestinal biopsy. Likewise, the positive predictive value was above 90% in patients with anti-tTG IgA levels greater than 3 times the upper limit of normal. These results are relevant, given that the study is the first to evaluate the clinical utility of anti-tTG IgA stratified by antibody elevation level for predicting intestinal villous atrophy in a Mexican population with confirmed celiac disease. The findings in this small group of Mexican celiacs support the no-biopsy diagnosis in adults with high anti-tTG IgA levels and are similar to those reported in other populations.10 The clinical decision to proceed with a no-biopsy diagnostic approach is complex and should take the informed opinion of the patient into account, among other aspects.1 From a practical viewpoint, no-biopsy diagnosis has obvious advantages, such as its noninvasive approach, easy access, low cost, rapid turnaround time, high patient acceptance, and good diagnostic accuracy.11 However, the global positioning of no-biopsy diagnosis in adults will depend on the results of prospective studies and the clinical application of new noninvasive diagnostic technologies, such as the whole blood assay measuring interleukin-2 (WBAIL-2) and other blood tests mainly targeting gluten-specific T cells.12 I believe that intestinal biopsy will continue to play an essential role in the diagnosis of celiac disease; perhaps some of its current limitations could be overcome through the use of novel methods, such as artificial intelligence, the precise automated measurement of histologic references, or even the use of proteomics for objectively evaluating intestinal biopsy.11 The recent history of celiac disease diagnosis is characterized by continuous change, supported by the creation of new evidence, as summarized by John Maynard Keynes in the famous quote attributed to him, “When the facts change, I change my mind. What do you do, sir?”.