AIM: To determine if TSPAN1 overexpression is associated with clinicopathological and prognostic factors in human colorectal adenocarcinoma. METHODS: Total RNA was extracted in 20 human adenocarcinoma tissues for TSPAN1 mRNA assay by RT-PCR. Eighty-eight specimens of human colorectal adenocarcinoma were surgically removed. TSPAN1 protein levels in cancer tissues were determined by immunohistochemistry using a polyclonal antibody against self-prepared TSPAN1. The correlation between TSPAN1 expression and the clinicopathological factors and the overall survival rate was analyzed by univariate and multivariate assay. RESULTS: TSPAN1 mRNA was detected in 90.0% (18/20) of cancerous tissues. The light density of TSPAN1 mRNA expression levels was 0.89 ± 0.30 in adenocarcinoma by gel-image system. TSPAN1 protein expression was detected in 78.41% (69/88) and weakly expressed in 40% normal colorectal tissues. There were significant differences between colorectal adenocarcinoma and normal control epithelium ( P < 0.05). TSPAN1 protein expression in colorectal cancerous tissue was significantly correlated with the histological grade, cell expression PCNA, lymph nodal metastasis and TNM staging of the disease. Patients with TSPAN1 protein overexpression had a significantly shorter survival period than that in patients with TSPAN1 protein negative or weak expression, respectively ( P < 0.05). Furthermore, by multivariate analysis, TSPAN1 protein expression demonstrated an independent prognostic factor for human colorectal cancers ( P < 0.05, relative risk 0.755; 95% confidence interval 0.302-1.208). CONCLUSION: The expression of TSPAN1 gene is increased in colorectal carcinoma, suggesting that TSPAN1 might serve as an independent prognostic factor for the colorectal adenocarcinoma patients.