Excision Repair Cross-Complementing Rodent Repair Group 2 (ERCC2) plays an important role in DNA repair by eliminating bulky DNA adducts produced by platinum agents during the nucleotide excision repair pathway. Several studies have associated polymorphisms in ERCC2 with response to platinum therapy, lung cancer risk, and DNA repair capacity. This study examined ERCC2 polymorphisms and haplotype structure across 18.9 kb in 95 European, 95 African, and 95 Asian individuals. Single-nucleotide polymorphisms (SNPs) (ERCC2 -9164 A>T, -1989 A>G, -516 G>A, 468 C>A [Arg156Arg], 1737 C>T [Val579Val], 2133 C>T [Asp711Asp], and 2251 T>G [Lys751Gln]) were mined and mapped using Golden Path, PolyMAPr, and Promolign. Genotyping was performed using PCR and pyrosequencing. Allele frequencies ranged from 0 to 0.47 (Europeans), 0.05 to 0.72 (Africans), and 0 to 0.47 (Asians). The synonymous cSNP at codon 579 could not be confirmed in our populations. There were significant differences in haplotype structure and frequency between populations. This information on ERCC2 genomic structure will allow the construction of definitive studies to clarify the clinical role of this important gene.