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Clinical isolates of Staphylococcus aureus (n = 276) were collected in 10 different hospitals located in the Southwest (cities of Ibadan and Lagos) and North-Central (city of Jos) parts of Nigeria. Resistance profiling of these strains revealed that the vast majority was still susceptible to methicillin (98.6% MSSA). Pulsed field gel electrophoresis (PFGE) performed for these strains identified 45 different genotypes, nine of which were identified in four or more different hospitals. The major PFGE type (genotype 2) comprised 23% of all isolates. In addition, several other strains were shown to be endemic in individual hospitals. Three out of four multi-resistant MRSA strains that were detected were sequence type 8 (ST8) as determined by array-based multi-locus sequence typing (MLST). PCRs for cataloguing the staphylococcal cassette chromosome (SCCmec) type were negative for two of these, suggesting the existence of a new methicillin-resistance gene complex in the ST8 genetic background. In conclusion, major clones of MSSA circulate in Nigeria, and the MRSA incidence is still low. However, the occurrence of old and new versions of SCCmec in some of the ecologically abundant MSSA strains should be taken as a serious warning since clonal expansion of this type of strains is not unprecedented.