Here we report the downregulation of S100B in the nuclear proteome of the corpus callosum from nine schizophrenia patients compared to seven mentally healthy controls. Our data have been obtained primarily by mass spectrometry and later confirmed by Western blot. This is an intriguing finding coming from a brain region which is essentially composed by white matter, considering the potential role of S100B in the control of oligodendrocyte maturation. This data reinforce the importance of oligodendrocytes in schizophrenia, shedding more light to its pathobiology.