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S100B, a protein abundant in astroglial cells within the central nervous system, has been shown to increase in cerebrospinal fluid and serum after various neurologic diseases. However, the cerebral specificity of S100B has been questioned. This study aims to show serum S100B levels after uncomplicated bone fractures in patients without current or prior neurologic diseases.Blood for sampling was drawn from patients seeking care at the emergency department presenting with various uncomplicated orthopedic fractures no older than 24 hours and having no previous or suspected neurologic disorder or head injury.Fifty-five consecutive patients with acute fractures were included in the study. Serum S100B levels were raised above 0.15 μg/L in 16 of 55 (29%) patients (range, 0.02–0.51 μg/L; mean, 0.13 ± 0.11 μg/L).S100B levels were raised in 29% of patients with acute fractures without apparent cerebral injury, which suggests an extracerebral source of S100B. This information should be taken into account when interpreting S100B levels when dealing with brain damage.