ABCG2/BCRP confers resistance to cells against anticancer agents such as 7-ethyl-10-hydroxycamptothecin, topotecan, and mitoxantrone. Many single nucleotide polymorphisms (SNPs) of the ABCG2 gene have been reported. Nine (G34A, C376T, C421A, C458T, A616C, T1291C, T1465C, A1768T, G1858A) out of 20 exonic SNPs are nonsynonymous. A splicing variant ∆944-949 was also reported. Among them, C376T, found in 2-3% of Japanese population, is the most striking one because it substitutes stop codon for Gln-126, resulting in non-functional truncated protein. The second functional SNP is C421A, substituting Lys for Gln-141. C421A ABCG2-transfected mouse fibroblasts showed markedly decreased protein expression and low-level drug resistance compared with wild-type ABCG2-transfected cells when transfectants expressed similar levels of ABCG2 mRNA. C421A was found in 20-30% of Caucasians and 50-60% of Asians, respectively. G34A, substituting Met for Val-12, and ∆944-949, deleting Ala-315 and Thr-316, were not associated with significant alteration of the protein expression and drug resistance. Functional alteration caused by the other exonic SNPs has not yet been reported. People with the C376T and/or C421A alleles may express low amounts of ABCG2, resulting in alteration of bioavailability and sensitivity to ABCG2-substrate drugs. In this regard, two clinical studies have been reported. One showed the clinical importance of C421A SNP on pharmacokinetics of topoisomerase I inhibitor, but the other did not agree. Further investigation of subjects bearing C376T and/or C421A on the both alleles, that would express less than 20% of the protein of the homozygous wild-type carriers, will be needed to clarify clinical relevance of ABCG2 SNPs.