Protein S100B has been shown to increase in serum and cerebrospinal fluid (CSF) in various neurological diseases. However, the levels of S100B in conjunction with cerebral herniation have not been studied and the significance of extracerebral S100B has become an important issue. We report on a multi-trauma patient in whom cerebral herniation occurred 2 days after admission. Following this, organ-harvesting procedures were performed for transplantation. We measured serial serum S100B during both the ongoing herniation and the following extracerebral surgery. We found that S100B levels seemed to peak immediately prior to cerebral herniation and then decreased shortly thereafter and concluded that the source of the measured serum S100B in this patient was of predominately cerebral origin. In conjunction with the organ harvesting procedure S100B levels increased, indicating that extracerebral sources of the protein also exist.