Community Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen with increasing clinical significance. Initially recognized as a cause of skin and soft tissue infections, it has soon been shown to cause life threatening illnesses. We describe two cases of osteomyelitis of the femur in young otherwise healthy adults. Initially a preliminary diagnosis of osteosarcoma was suggested by radiologic studies and both patients underwent an excisional biopsy. Following identification of the pathogen as CA-MRSA (Panton-Valentine leukocidin positive USA300 clone), both patients were successfully treated with prolonged courses of vancomycin.