We compared a noninvasive serological test using a commercial immunoblot assay (Helicoblot 2.0) to tissue-based methods [rapid urease test (CLO test), histology and culture] in eighty Thai patients undergoing upper endoscopy. A true positive test was defined as at least two of the biopsy-related tests being positive. The CLO test was the most accurate test with sensitivity and specificity as high as 100%, whereas histology and culture had sensitivity of 100% and 72.2%, respectively, and the specificity of 72.7% and 96%, respectively. The serological test had a high sensitivity (97.2%) but exhibited an unsatisfactory specificity (40.9%). We concluded that the rapid urease test using multiple gastric biopsies was the most appropriate method for diagnosing H. pylori status. The role of immunoblot assay as a serological screening test in our population remains doubtful, but it may identify patients who have been infected with certain strains of H. pylori.