Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, usually being acquired during childhood, and its persistence into adulthood represents one of the main contributors of gastric carcinogenesis. Based on these statements, it would be of great importance to know if the most early premalignant transformation occurs in children or later since, this would enable the development of effective anti-tumorigenesis strategies. The interplay between H. pylori virulence factors, the host’s responses modified by this infection, and the gastric microecology are complex and eventually lead to the development of gastric cancer in susceptible individuals. Several biomarkers were identified as major contributors of this long-lasting process, such as pepsinogens, gastrin 17, lipid-, glucose- and iron-metabolism parameters, immunity players, aberrant bacterial DNA methylation, H. pylori virulence factors, and hallmarks of gastric dysbiosis. Several of these biomarkers were also identified in children with H. pylori infection, independently of the presence of premalignant lesions, which were also proven to be present in a subgroup of H. pylori-infected children, especially those carrying extremely virulent strains. Therefore, the most incipient premalignant gastric changes might indeed occur early during childhood, opening a promising research gate for further studies to delineate the border between infection and cancer.