A comparative population genetics study revealed high levels of nucleotide polymorphism and intermediate-frequency alleles in an arcC gene of Staphylococcus epidermidis, but not in a homologous gene of the more aggressive human pathogen, Staphylococcus aureus. Further investigation showed that the arcC genes used in the multilocus sequence typing schemes of these two species were paralogs. Phylogenetic analyses of arcC-containing loci, including the arginine catabolic mobile element, from both species, suggested that these loci had an eventful history involving gene duplications, rearrangements, deletions, and horizontal transfers. The peak signatures in the polymorphic S. epidermidis locus were traced to an arcD-like gene adjacent to arcC; these signatures consisted of unusually elevated Tajima’s D and π/K ratios, which were robust to assumptions about recombination and species divergence time and among the most elevated in the S. epidermidis genome. Amino acid polymorphisms, including one that differed in polarity and hydropathy, were located in the peak signatures and defined two allelic lineages. Recombination events were detected between these allelic lineages and potential donors and recipients of S. epidermidis were identified in each case. By comparison, the orthologous gene of S. aureus showed no unusual signatures. The ArcD-like protein belonged to the unknown ion transporter 3 family and appeared to be unrelated to ArcD from the arginine deiminase pathway. These studies report the first comparative population genetics results for staphylococci and the first statistical evidence for a candidate target of balancing selection in S. epidermidis.