Background: Non-invasive methods are advisable for the detection of Helicobacter pylori- related chronic gastritis in pediatric patients. Serum pepsinogens I and II (sPGII and sPGII), gastrin-17 (G-17) and anti-H. pylori antibodies (IgG-Hp) have been proposed as a ‘serological gastric biopsy’. Aim: To assess H. pylori infection and to evaluate gastric mucosa status in a pediatric population by means of serological parameters such as sPGI, sPGII, G-17 and IgG-Hp. Methods: 45 consecutively children evaluated for upper gastrointestinal symptoms were analyzed. All children were submitted to upper gastrointestinal endoscopy with biopsies. Serum samples were analyzed for IgG-Hp, sPGII, sPGI and G-17 (Biohit, Helsinki, Finland). Results: 18 children had H. pylori- related mild or moderate non-atrophic chronic gastritis. They presented significantly higher mean levels of sPGII and of IgG-Hp than negative ones, eitherunder or up to 10 years. sPGI showed significantly increased levels in H. pylori- positive patients only over 10 years. G-17 levels were not different between H. pylori- positive and -negative ones. The best cut-offs of IgG-Hp, sPGII and of product IgG-Hp·sPGII, to identify H. pylori infection, were 30 IU/l, 9 µg/l, and 241 IU/l·µg/l, respectively. The product IgG-Hp·sPGII identified H. pylori infection with a 100% sensitivity, 92% specificity, 90% positive predictive value and 100% negative predictive value. IgG-Hp and IgG-Hp showed a correlation (r = 0.94; p < 0.001). Conclusions: Combined analysis of sPGII and IgG-Hp antibody levels could be recommended as a non-invasive panel for the assessment of H. pylori- related histological alterations of gastric mucosa in childhood.