Background: Clinically relevant polymorphisms often demonstrate population-specific allele frequencies. Central and South America remain largely uncategorized in the context of pharmacogenomics. Materials & methods: We assessed 15 polymorphisms from 12 genes (ABCB1 3435C>T, ABCG2 Q141K, CYP1B1∗3, CYP2C19∗2, CYP3A4∗1B, CYP3A5∗3C, ERCC1 N118N, ERCC2 K751Q, GSTP1 I105V, TPMT 238G>C, TPMT 460G>A, TPMT 719A>G, TYMS TSER, UGT1A1∗28 and UGT1A1 -3156G>A) in 81 Peruvian and 95 Mexican individuals. Results: Six polymorphism frequencies differed significantly between the two populations: ABCB1 3435C>T, CYP1B1∗3, GSTP1 I105V, TPMT 460G>A, UGT1A1∗28 and UGT1A1 -3156G>A. The pattern of observed allele frequencies for all polymorphisms could not be accurately estimated from any single previously studied population. Conclusion: This highlights the need to expand the scope of geographic data for use in pharmacogenomics studies.