To determine the percentage agreement between serology and histology for detection of Helicobacter [H.] pylori infection. Cross-sectional analytical study. Department of Pathology and Microbiology, The Aga Khan University and Hospital, Karachi, from January to December 2009. Fifty subjects were selected by non-probability purposive sampling from laboratory data who had serological testing of H. pylori IgG antibody, prior to histological evaluation of endoscopic gastric or/and duodenal biopsies. Serological Quantification of H. pylori IgG was carried out with HpG screen ELISA kit [Genesis Diagnostics, UK], using an enzyme linked immunosorbent assay for detection of IgG antibodies against H. pylori. Manufacturer’s recommended cutoff value was used and results were considered positive when greater than 7 U/ml. For histological diagnosis, an expert histopathologist characterized the presence of spiral bacteria in the mucosal layer or the surface of epithelial cells on microscopic examination, as a positive test. An agreement of 0.72 was found by Kappa statistics between serology and histopathology results and a good diagnostic accuracy [86%] of serological testing was observed for the diagnosis of H. pylori infection. A substantial agreement was found between serology and histopathology results to detect the H. pylori infection. Laboratory-based serologic testing using ELISA technology to detect IgG antibodies is inexpensive, noninvasive and convenient method to detect the H. pylori infection in primary care setting.