Low-grade gastric lymphomas of mucosa-associated lymphoid tissue (MALT) may be extremely difficult to differentiate from atypical lymphoid infiltrations of the gastric mucosa caused by Helicobacter pylori (H. pylori) infection, especially if lympho-epithelial destructions are not detected. In order to clarify this diagnostic problem and to evaluate the potential benefit of clearing H. pylori-induced lymphoid infiltration a prospective study was performed. Our study included biopsy specimens from 61 patients, that showed excessive lymphoid infiltrations. Using histology and immunohistochemistry no definite diagnosis could be delivered. In 46 (76.4%) cases histological regression occurred 4 weeks after the end of therapy suggesting a reactive infiltrate. In 7 patients (11.5%) the histological picture remained unchanged, and in 8 (13.1%) the follow-up biopsies revealed lympho-epithelial destructions allowing the diagnosis of low-grade MALT lymphoma. On the basis of our data we conclude that eradication of H. pylori could provide an additional tool in the differential diagnosis between atypical lymphoid infiltrations of the gastric mucosa caused by H. pylori and an early primary gastric MALT lymphoma.