Acute osteomyelitis (AO) in neonates, although rare, represents a diagnostic and therapeutic challenge. A high index of suspicion is necessary to make an early diagnosis, and the observation of clinical signs is crucial. The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is an emerging problem in pediatrics. In neonates, MRSA infections can cause a wide spectrum of diseases including bone and joint infections. We report two cases of AO in full-term neonates, with no risk factors, due to MRSA.