Coagulase-negative staphylococci (CNS) are increasingly recognized to cause clinically significant infections, with S. epidermidis often cited as the third most common cause of nosocomial sepsis. Among CNS, there is a high prevalence of methicillin resistance associated with staphylococcal cassette chromosome (SCCmec) elements. Although identical SCCmec types can exist in S. aureus and CNS, some novel classes of SCCmec may be unique to CNS. Differences in the accuracy of identification of CNS species and use of non-standardized methods for the detection of methicillin resistance have led to confusing data in the literature. In addition to the review of SCCmec in CNS, in this paper we report a 2-year surveillance of methicillin-resistant CNS in a tertiary-care hospital in Guadalajara, Mexico.