PURPOSE:Currently, studies on serologic diagnosis of Helicobacter pylori-associated gastric cancer (GC) in Latin America are scarce. The aim of the present study was to evaluate the association between H. pylori serology tests in patients with early precancerous lesions or GC, when compared with non-atrophic gastritis in Colombia, Paraguay, and Mexico, three countries in Latin America with a high prevalence of H. pylori infection but contrasting rates of GC mortality. METHODS:Gastric biopsies and blood samples were obtained from patients attending the gastroenterology or oncology services of hospitals in the three participating countries. IgG antibodies against H. pylori whole-cell antigens and CagA were tested in 1,117 sera using an enzyme-linked immunoabsorbent assay. RESULTS:Positive and significant associations were shown for H. pylori seropositivity and preneoplastic lesions in Mexico (OR 2.0; 95 % CI 1.1-3.4) but not in Colombia (OR 1.2; 95 % CI 0.6-2.1) or Paraguay (OR 1.5; 95 % CI 0.6-3.2); no significant associations were shown for GC in any country. CagA seropositivity was associated with preneoplasic lesions in all three countries (ORs = 2.1, 3.0, and 3.1 for Mexico, Colombia, and Paraguay, respectively), and with GC only in Colombia (OR 4.3; 95 % CI 2.1-9.2). CONCLUSIONS:In countries of Latin America, the IgG CagA test might be a useful biomarker for patients with gastric preneoplastic lesions and for those at risk of developing gastric cancer.