Both HLA-DQA1 and -DQB1 genes and Helicobacter pylori infection have been linked to gastric cancer. The aim of this work was to determine if HLA-DQA1 and -DQB1 alleles are presented at altered frequency in Italian patients with gastric adenocarcinoma and H. pylori infection. Oligotyping for HLA-DQA1 and -DQB1 and H. pylori serology was performed for 50 patients with gastric adenocarcinoma and compared with 80 patients with colonic adenocarcinoma and 179 healthy subjects. H. pylori infection was present in 76% of gastric cancer patients, 77.5% of colonic cancer patients, and 72% of controls. The prevalence of infection was not significantly different in the three groups of subjects sorted according to their HLA-DQA1 or -DQB1 status. Apart from HLA-DQA1* 0201, which was less common in patients with colonic carcinoma than controls, no other HLA-DQA1 and no HLA-DQB1 allele were present at altered frequency in patients with gastric or colonic cancer. Neither anatomical location and histological type of cancer nor the presence of lymph node or distant metastases were significantly associated with specific HLA-DQA1 or -DQB1 alleles or H. pylori infection. Both HLA-DQA1 and -DQB1 genes have a minor, if any, role in H. pylori infection and gastric carcinogenesis.