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Background: In Padova and Vienna International Classification, the usual intestinal metaplasia (UIM) of the stomach,including complete and incomplete type, is defined as negative for dysplasia, and hyperproliferative intestinal metaplasia (HIM) as indefinite for dysplasia, but the biological characteristics of these two types of intestinal metaplasia (IM)remain to be studied. Objective: To investigate the biological differences between UIM, HIM and intestinal type gastric cancer (IGC), apanel of biomarkers were detected. Methods: A total of 38 cases of IGC, 41 HIM and 56 UIM adjacent to gastric cancer were studied. Immunohistochemistry was used to detect the expressions of pS2, MUC2, MUC5AC, MUC6, Ki-67, EGFR, p53 and sulfo-Lewisa in UIM, HIM and IGC. Microsatellite instability (MSI) in UIM, HIM and IGC was detected by using Denaturing High Performance Liquid Chromatography (DHPLC). Results: The pS2 antigen expression in UIM (78.6%) was significantly higher than in HIM and IGC (9.8%, 10.5%), p＜0.01. The MUC6, sulfo-Lewisa and EGFR protein expressions were significant increased in HIM (24.4%, 82.9%, 48.7%) and IGC (34.2%, 75.0%, 42.1%) than in UIM (3.6%, 25.5%, 17.9%), p＜0.01. Areversed pattern of expressions of MUC2 and MUC5AC was observed in UIM (96.4%, 50.0%) and HIM (82.9%, 36.6%)compared with IGC (52.6%, 13.2%), p＜0.05; and the p53 gene expression was increased from UIM (1.8%) to HIM (19.5%) to IGC (57.9%), p＜0.01. The Ki-67 labeling index was significantly different among three lesions (UIM: 16%±6%, HIM:45%±9%, IGC: 63%±10%, p＜0.01). Conclusion: These findings suggest that there are different bio-characteristics among UIM, HIM and IGC, and HIM may have higher potential to progress to more advanced lesions in comparison with UIM.