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To explore whether variations in odontogenesis-related genes are associated with tooth-size discrepancies. Measurements of the width of permanent teeth were obtained from dental casts of 62 orthodontic patients (age 15.65 ± 6.82 years; 29 males and 33 females). Participants were classified according to the anterior and overall Bolton ratios as without tooth-size discrepancy or with maxillary or mandibular tooth-size excess. Genomic DNA extracted from buccal cells was used, and 13 single nucleotide polymorphisms (SNPs) across nine genes were genotyped by polymerase chain reaction using TaqMan chemistry. χ2 or Fisher exact tests were applied to determine the overrepresentation of genotypes/alleles depending on the type of tooth-size discrepancy (α =.05; corrected P value: P < 5.556 × 10−3). Odds ratios (ORs) and their correspondent 95% confidence intervals (CIs) were also calculated to investigate the risk of this phenotype for the SNPs having significant association. Individuals carrying the FGF10 rs900379 T allele were more likely to have larger mandibular teeth (OR = 3.74; 95% CI: 1.65–8.47; P =.002). This effect appeared to be stronger when two copies of the risk allele (TT) were found (recessive model, OR = 6.16; 95% CI: 1.71–22.16; P =.006). On the other hand, FGF13 rs5931572 rare homozygotes (AA, or male A hemizygotes) had increased risk of displaying tooth-size discrepancies when compared with the common homozygotes (GG, or male G hemizygotes; OR = 10.32; 95% CI: 2.20–48.26; P =.003). The results suggest that FGF10 and FGF13 may contribute to the presence of tooth-size discrepancies. [ABSTRACT FROM AUTHOR]