A single nucleotide polymorphism (SNP) -420C > G of the resistin gene was screened in 248 colorectal cancer (CRC) patients and 256 controls. No significant difference in genotype distribution was found. However, we found an upregulation in 92% of the samples in the levels of resistin protein in cancer tissue (n = 83). Immunohistochemical analysis revealed heterogenous staining of resistin predominantly in the cancer tissue. Further, resistin induced secretion of MMP-2 and MMP-9 from monocytes. The results of this study suggest that resistin may play a partial role in CRC but that the -420C > G resistin polymorphism is not a potential genetic susceptibility factor.