Stanniocalcin 2 (STC2) is a novel member of the Stanniocalcin family, the function of which remains unclear. Its expression is clinically significant in several cancers. The aim of this study was to evaluate the clinical value of measuring expression levels of STC2 in colorectal cancer (CRC) patients. A total of 47 tumor and matched tumor-free margin samples were obtained during surgery. The STC2 mRNA expression level in tumor and marginal tissue was examined by real-time quantitative PCR. STC2 mRNA expression levels were higher in tumor tissues than the control. (r=0.36, p≤0.02). mRNA expression level of STC2 was significantly associated with tumor size (p≤0.05) and histologic grade (p≤0.05). Our study demonstrated that STC2 was significantly expressed in CRC patients, relative to the control. STC2 can therefore be used as a biomarker to differentiate between tumor borders and margins. Analysis of STC2 gene expression during surgery could be useful in reducing surgical error in tumor removal and increasing overall success of surgery with improved tumor clearance. However, in some cases such as where the tumor is end-stage, the expression of such a biomarker may not be clinically beneficial to record. The consideration of marginal samples as a control group can help reduce the effect of confounding factors such as racial and individual differences.