The diagnosis of celiac disease (CD) remains a clinical challenge based on the incomplete specificity and sensitivity rates of current non-invasive tests. Furthermore, histological assessments fail to identify all overt cases and, in particular, do not manifest pathognomonic alterations in silent cases. Accordingly, the majority of CD cases are diagnosed with great delay. Recent research into the pathogenesis of CD, allowed us to identify a neo-antigen that appears to be the most promising serological tool for the detection of anti-tissue transglutaminase as well as anti-gliadin antibodies.