Celiac disease (CD) is an autoimmune enteropathy triggered by ingestion of gluten in genetically susceptible subjects and is one of the most frequently occurring, treatable, lifelong disorders. In this disease we recognize the trigger (gluten), the genetic factor (HLA DQ2/8), the auto-antigen (the tissue-transglutaminase enzyme) and the auto-antibodies (IgA-IgG anti-transglutaminase) which are produced by the intestinal mucosa B lymphocytes (Gastroenterology 2000;119:234, J Immunol 2001;166:4170). Undetected or untreated, CD may cause more severe complications later in life, such as autoimmune disorders. Clear evidence exists of gluten-related autoimmunity in genetically predisposed patients (presence of the HLA DQ2/8). It has been shown that autoimmune disorders involving organs other than intestine (such as pancreas, cerebellum, liver, skin) could develop in unrecognized and/or untreated celiac subjects because of a persistent exposure to gluten. Presently, the additional risk for autoimmune diseases is estimated at 1.1% for each year without diagnosis (Gastroenterology 1999;117:297). Furthermore, when on a diet containing gluten, some CD patients produced organ-specific auto-antibodies (GAD, ICA, TPO, anti-Purkinje cells, cardiac auto-antibodies) which were not CD related and which disappeared after 6 to 12 months of gluten-free diet (J Pediatr 2000;137:263; Lancet 1996;347:369; Circulation 2002;105:2611). Bearing these data in mind, an early diagnosis of CD might have prevented some CD patients from developing an autoimmune disease such as type 1 diabetes or thyroiditis. In view of these observations, it is recommended for subjects with autoimmune diseases or at risk for CD to be screened for CD and to repeat serological screening about every three years to detect cases of clinically silent, late-onset CD. In other words, there are gluten-genetically predisposed subjects (tested positive for HLA DQ2/8) - testing negative for serum anti-tTG - that become antibody-positive later in life. The tTG-targeted antibodies bound locally to tissue transglutaminase may be present in diseased organs before they become detectable in the circulation, thus accessible for serological testing. The intestinal mucosa in the early phases is characterized by normal villi including a normal number of intraepithelial lymphocytes. The process of mucosal deterioration may take years or even decades (Am J Gastroenterol 2000;95:463) and a long follow-up without treatment may sometimes be harmful. Symptoms are not related solely to villous atrophy, and many proven early celiac disease cases had suffered from gluten-dependent gastrointestinal symptoms even before the villous atrophy developed (Gut 2006;55:133, Scand J Gastroenterol 2005;40:564, Gut 2004;53:641, Scand J Gastroenterol 1998;33:944, Acta Paediatr 1995;84:1252, Gastroenterology 1993;104:1263).