The differential diagnosis of schizophrenia (SZ) and bipolar disorder (BD) is based solely on clinical features and upon a subset of overlapping symptoms. Within the last years, an increasing amount of clinical, epidemiological and genetic data suggested inconsistent with the Kraepelinian dichotomy. We performed re-analysis of genome-wide gene expression data obtained from postmortem prefrontal cortex (PEC) of both BD and SZ patients with matched controls from four independent microarray experiments. We found 2,577 and 477 genes specifically altered in BD and SZ, respectively. Of these, 164 genes were shared between the syndromes. We identified genes of the transcriptional and post-transcriptional machineries altered in BD and genes of the development changed in SZ. Our results showed that the genomic expression profile of BD and SZ had some similarity but still could be well-distinguished by suitable statistical test.