Interpatient variability in pharmacokinetics (PK) of sunitinib is high. Single nucleotide polymorphisms (SNPs) in PK candidate genes have been associated with sunitinib efficacy and toxicity. Whether these SNPs truly affect sunitinib PK remains to be elucidated. This multicenter study in 114 patients investigated whether SNPs and haplotypes in genes encoding metabolizing enzymes or efflux transporters are related to the clearance of sunitinib and its active metabolite SU12662. SNPs were tested as covariates in a population PK model. SNPs in CYP3A4, CYP3A5 and ABCB1 were related to clearance of sunitinib and SU12662 in univariate analysis. In multivariate analysis, CYP3A4*22 was lastly eliminated with an effect size of -22.5% on clearance. Observed effect sizes are below the interindividual variability in clearance and are therefore too limited to directly guide individual dosing of sunitinib.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 24 February 2014. doi:10.1038/clpt.2014.47.