ATP-binding cassette (ABC) transporters actively export a wide variety of molecules from cells, contributing to reduce the local cellular burden of toxic compounds. ABCG2/BCRP is abundantly expressed in epithelial cells of the intestine and colon. The expression and activity of this transporter in the gut differ between individuals, due at least in part to genetic polymorphisms, which may thus affect the risk of colorectal cancer (CRC). We selected 15 tagging SNPs, covering all the known genetic variation of the gene, and typed them in 680 CRC cases and 593 controls. We found that heterozygous carriers of the minor alleles of SNPs rs2622621 and rs1481012 had a decreased risk of CRC, respectively, with odds ratios of 0.73 (95% confidence interval 0.56-0.94; P(value)=0.017), and 0.72 (95% CI 0.53-0.97; P(value)=0.03). Thus, we found no strong and clearcut association between ABCG2 polymorphisms and CRC risk. To our knowledge this is the first report on ABCG2 and CRC risk.