The glycoprotein Chromogranin A (CgA) is expressed by endocrine and neuroendocrine cells. High levels of serum CgA serve as marker of neuroendocrine tumors (NET), but its role in autoimmunity has not been assessed.Investigate CgA utility as marker of endocrine autoimmunity.CgA serum levels were evaluated in 807 consecutive unselected subjects (cross-sectional study) with the Time-Resolved Amplified Cryptate Emission Technology.Serum CgA concentrations were increased in 66%, 39%, 38%, and 24% of patients with NET, type 1 diabetes (T1D), autoimmune gastritis (AG) and autoimmune polyendocrinopathy (AP), respectively. Compared to healthy controls (C), the odds of positive CgA measurement were up to 28 times higher in the disease groups. In detail, odds ratios for positive CgA levels were 27.98, 15.22, 7.32 (all p<0.0001), and 3.89 (p=0.0073) in patients with NET, T1D, AG and AP, respectively. In AG, CgA and serum gastrin correlated positively (r =0.55, p<0.0001). The area under receiver operating characteristic curve to predict AG was higher for parietal cell antibody (PCA) positivity than for CgA (0.84 versus 0.67, p<0.0001). However, in combination with PCA and intrinsic factor autoantibodies, CgA independently improved prediction of AG (odds ratio 6.5, p=0.031). An impact of age on CgA positivity and on CgA value was detected (p<0.0001) while current smoking significantly increased CgA serum levels by 25% (p=0.0080).CgA qualifies as a novel biomarker for T1D, AP, and AG.