To elucidate the evolutionary process of the nervous system (NS) in metazoa, we examined the relationship between human genes specifically expressed in the NS (NS-specific genes) and the time of their evolutionary emergence. We obtained 255 human NS-specific genes from the gene expression data of the human full-length cDNA annotation invitational (H-invitational) database. To determine when these genes emerged for the first time during evolution, we searched for orthologues of the 255 NS-specific genes in 13 species (excluding human) by homology searches against their complete genome sequences. We found that 14% of the NS-specific orthologous genes had already emerged before the divergence between yeast and human. This finding suggests that a common ancestor, which should have no nervous system, already possessed a portion of the genes homologous to human NS-specific genes, implying that 14% of the NS-specific genes should have changed differentially their original functions during evolution. If this is the case, then the remaining 86% of the 255 NS-specific human genes have newly emerged during evolution. In particular, we found that the largest portion (24%) of the 255 NS-specific genes had emerged after divergence of urochordata and human but before divergence of fishes and human. These results suggest that the main cause of the NS evolution was the addition of new genes which took place most actively just before or at the evolutionary emergence of vertebrates.