Most patients affected by celiac disease (CD) are asymptomatic or hyposymptomatic and undiagnosed, and are at risk of preventable complications. Therefore, early diagnosis is highly recommended. Multiple diagnostic antibodies are available; the most frequently used is IgA to tissue transglutaminase (IgA-tTg). It may yield false results and, alone, does not address IgA deficiency. Recently, a new generation of anti-neo-epitope tTg check (IgG + IgA) has become available. It is highly sensitive and specific, covers IgA-deficient patients with CD, reflects intestinal damage, and has predictive potential in the diagnosis of CD.