Objective Helicobacter pylori is generally considered a noninvasive colonizer in the stomach. The intracellular localization of H. pylori has been reported in cultured cell lines. However, whether H. pylori invades human gastric epithelial cells in vivo, and whether this invasion, if present, contributes toward the pathogenesis of peptic ulcer disease remain controversial.Patients and methods Gastric endoscopic biopsies were obtained from 20 patients with upper gastrointestinal symptoms and a positive rapid urease test, and five control participants. The location of H. pylori and the associated mucosal changes were assessed using electron microscopy.Results Adherence of H. pylori to the cell surface was detected in 80% of cases and was categorized into three main patterns: fibrillar-like strands, adhesion pedestals, and membrane fusion. H. pylori were found within the cell cytoplasm in 77.78% of cases with ulcer disease versus 18.18% of cases with gastritis (P = 0.022). Both coccoid and bacillary forms could be detected intracellularly. Internalization appeared to occur in a stepwise manner. A novel finding was the observation, in one case with ulcer disease, of an intraepithelial colony of coccoid H. pylori.Evidences of cell injury included disruption of microvilli and cytoplasmic vacuolar degeneration, which was more prominent in cells with internalized bacteria compared with cells with bacteria only on the surface.Conclusion This study confirmed the existence of intracellular H. pylori, both coccoid and bacillary forms, in gastric endoscopic biopsies. The more prominent cell injury associated with internalization of H. pylori and the higher incidence of intracellular organisms in ulcer patients suggest that internalization of H. pylori does play a role in the pathogenesis of peptic ulcers.