Changes of cerebral cortex size and brain volume have experienced evolutionary expansion across mammals, which is the cellular base of neuronal network complexity. The existence of cortex folding, allowing huge area of cortex to fit into a relatively small cranial space, is one of important evolutionary features in primate. The adult human CNS contains approximately 86.1 billion neurons and equal number of glial cells. Among which, human cerebral cortex consists of roughly 16.34 billion neurons. Based on algorithm analysis, approximately 3.86 million projection (excitatory/pyramidal) neurons are generated per hour during prenatal cortical neurogenesis in human. Such an incredible fast speed of neurogenesis suggests that human neocortex development requires strictly organized molecular regulations and cellular processes. Here we discuss the molecular and cellular characteristics of mammalian cerebral cortex expansion and the related disease.