Laser microdissection (LMD) and microarray were used to identify genes associated with colorectal cancer. Stanniocalcin 2 (STC2) expression and clinicopathological significance in 139 clinical colorectal cancer samples were specifically investigated using real-time quantitative reverse transcription-polymerase chain reaction. A number of genes upregulated in colorectal cancer cells compared to normal colorectal epithelial cells were identified including STC2. STC2 gene expression in cancer tissue was higher than in corresponding normal colorectal epithelial tissue in 124 of 139 cases (89.2%, p < 0.01). Tumors with high STC2 expression showed higher frequencies of lymph node metastasis, lymphatic invasion, tumor depth, tumor size and AJCC Stage classification (p < 0.01). Patients with high STC2 expression also showed significantly worse overall survival rates than those with low STC2 expression (p < 0.01). Furthermore, STC2 gene appeared to be associated with colorectal cancer progression and may be a useful prognostic indicator for colorectal cancer.