Lack of clinical biomarkers for early gastric cancer without specific early symptoms leads to delayed diagnosis, which contributes to high mortality of gastric cancer. Here, we used oligonucleotide microarray to systematically examine differential gene expression among 33 samples from normal, premalignant, and malignant lesions in stomach. A focal adhesion pathway mainly composed of collagen genes was found to have a significantly different expression profile in gastric cancers compared to premalignant lesions. A subset of collagen genes efficiently separated malignant from premalignant tissues, and two representative genes COL11A1 and COL1A1 were validated in 42 tissue samples with quantitative reverse transcription-PCR and in situ hybridization. The data above suggest that focal adhesion pathway may have a role in the pathogenesis of gastric cancer, and the expression profile of collagen genes may be a potential biomarker to distinguish malignant from premalignant lesions in stomach.