Surgical site infections (SSI) are the most common complications of breast cancer surgery. The authors identified 35 cases of SSI in the M.D. Anderson Cancer Center (Houston, TX) over a 7-month study period. Monomicrobial infections predominated (69%) with Staphylococcus aureus being isolated most often. A wide variety of gram-positive and gram-negative organisms were isolated from the 31% of polymicrobial infections, suggesting the need for broad-spectrum coverage at least until culture results become available. Although all S aureus isolates were susceptible to vancomycin (minimal inhibitory concentration [MIC] ≤ 2.0 µg/mL), 63% of methicillin-susceptible isolates and 82% of methicillin-resistant isolates had MIC values of ≥ 1.0 µg/mL for this agent, indicating the need for alternative therapeutic agents. The organisms were susceptible to trimethoprim/sulfamethoxazole, rifampin, linezolid, daptomycin, and tigecycline.