The S100 protein family constitutes the largest subgroup of the Ca binding proteins. To date 20 members of the family were discovered. S100 proteins regulate intracellular processes such as cell growth and motility, cell cycle regulation, transcription and differentiation. S100B protein is expressed constitutively by brain astrocytes. Serum S100B protein concentration in Stage II-III-IV melanoma is a reliable prognostic marker. The serum level of S100B protein is significant independent prognostic marker in respect to disease specific survival, it is a relevant marker for therapy monitoring and patient follow-up. It is recommended to determine the S100B expression pattern and intensity of the primary tumour of melanoma before therapy monitoring. Elevated S100B levels were published after head trauma, subarachnoidal haemorrhage and stroke. Furthermore, it indicates blood-brain barrier dysfunction. S100B protein was used to determine the cerebral damage after cardiovascular surgery as well.