Considering the important role of RNF43 in gastric homeostasis and the high frequency of mutations observed in gastric tumors, as well as the carcinogenic potential of H. pylori infection, in the present study we sought to investigate how chronic H. pylori infection would affect the onset and development of gastric pathology in mice carrying mutated Rnf43. Our results show that H. pylori infection worsens gastric pathology of RNF43H292R/H295R mice and suggest that RNF43 mutations in combination with sustained chronic inflammation contribute to the development of gastric malignancies. This evidence concerns the gene RNF43 and gastric neoplasm.