Objective: Cross-resistance is an important issue for macrolide, lincosamide and streptogramin B (MLSB) antibiotics. The erm genes alter their ribosomal binding site by encoding ribosomal methylases. Phenotypic presentation of erm-mediated resistance can be inducible (iMLS(B)) or constitutive (cMLS(B)). Expression of msr genes which encode active efflux pumps confers the MSB phenotype. In this study, we investigated the frequency of MLSB resistance phenotypes and the presence of erm and msr genes in clinical Staphylococcus isolates. Material and Methods: The frequency of MLSB resistance phenotypes were investigated using D-zone test in 731 clinical Staphylococcus strains. The presence of erm and msr genes was investigated by polymerase chain reaction in macrolide-resistant strains. Results: Of the investigated isolates, 37.3% had iMLS(B), 35.8% had cMLSB, and 26.9% had MSB phenotypes. Among studied, 45.9% of the strains carried ermC, 15.5% carried ermA, and 4.2% carried ermA and ermC genes. Phenotypic presentation of 51.4% of the erm gene carriers were iMLS(B) and 48.6% were cMLS(B). Of the MSB phenotype strains, 73.3% carried the msrA+msrB gene combination and 3.3% carried msrB alone. Various erm and msr gene combinations were determined in 13.7% of the isolates of which 54.3% expressed iMLS(B) or cMLS(B) phenotypes and 45.7% expressed the MSB phenotype. MSB phenotype and gene combination frequencies were more in coagulase-negative staphylococci (CoNS). Conclusion: Investigating genes conferring resistance to lincosamides is important for reducing the risk of treatment failure especially for erythromycin resistant, clindamycin susceptible strains. Due to the increasing resistance problem in staphylococcal infections, clinicians must be aware of resistance development while prescribing MLSB antibiotics.