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The objective of the present retrospective study was to clarify the clinical course, major pathogens, and other infections associated with infected cephalohematoma.From January 1978 to December 2003, records of all newborns were reviewed for evidence of an infected cephalohematoma, based either on local signs of infection or a diagnostic tap that yielded pus. Patients were divided into two groups: those seen in the early period (1978–1990) and in the late period (1991–2003).Twenty-eight newborns with infected cephalohematoma were identified, 14 each in the early and late periods. The mean age at onset was 17.8 ± 13.9 days. The most common local findings were erythema (79%), increasing size of the hematoma (68%), and a fluctuant mass (46%), while fever (64%), poor appetite (39%) and irritability (18%) were the common systemic signs. Common laboratory findings included leukocytosis (82%) and an elevated C-reactive protein (61%). Escherichia coli was the most common pathogen (16 patients, 57%) and was isolated significantly more frequently in the late period (early period: 36%, late period: 79%, P < 0.05). Staphylococcus aureus was the second common pathogen (five patients, 18%). Ten patients (36%) had other associated infection: eight had sepsis, three had meningitis, and one had osteomyelitis. In the early period three patients (11%) died.Clinicians should be aware that cephalohematoma is a potential site of infection. The incidence of associated system infection is high and may result in mortality. Appropriate diagnostic and therapeutic measures should be undertaken promptly if there are infectious signs.