In the present study we give some direction on the selection of the most appropriate typing method(s) to be used for the characterization of Staphylococcus epidermidis, in view of the most recent findings on the evolution, population structure, and epidemiology of this species. In order to achieve this aim, quantitative assessment of the correlation of the results of three typing methods-pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and staphylococcal chromosomal cassette mec (SCCmec) typing, which target different regions of the chromosome that evolve at different rates-was performed. In order to evaluate the discriminatory ability and the strength and direction of the correlation of the different typing methods, Simpson's index of diversity (SID), the adjusted Rand coefficient (AR), and the Wallace coefficient (W) were calculated. PFGE was the most discriminatory method (SID ؍ 99%), followed by MLST (SID ؍ 90%) and SCCmec typing (SID ؍ 75%). The values of AR and W (0.10 < AR < 0.30; 0.50 < W < 0.75) indicated that the partition of the same isolate collection by PFGE, MLST, and SCCmec typing provided results that had only a poor correlation with each other. However, the information provided by the combination of PFGE and SCCmec enabled the prediction of the results obtained by MLST at the level of the clonal complex with a high degree of precision (W > 0.90). We propose that clones of S. epidermidis be defined by the combination of the PFGE type followed by the SCCmec type, which provides reliable information on the short-term epidemiology and the ability to predict with consistency long-term clonal evolution.In recent years, the development and extensive use of molecular typing methods based on the direct analysis of genomic polymorphisms have greatly improved the understanding of the evolutionary history, population dynamics, and patterns of dissemination of bacteria (14,37,38).The basic principle of epidemiological typing is that isolates of an infectious agent that belong to the same chain of transmission are clonally related; that is, they descend from a common ancestor. During their evolutionary history, isolates within a given species diversify through point mutations, recombination, or the acquisition/deletion of mobile genetic elements, giving rise to extensive genomic and phenotypic diversity. Since the rates for mutation, recombination, and transfer of mobile elements as well as environmental pressures vary from species to species, the typing method selected and the threshold of marker similarity used to define a clone need to be adjusted to the species under investigation. Furthermore, space and time also need to be considered when the optimal epidemiological markers are selected. Ideally, typing methods should be reproducible and stable; should have a high discriminatory power and epidemiological concordance; should be versatile, easy to perform, easy to interpret; and should be cost-effective and time effective.Staphylococcus epidermidis is one of the most impor...