The neocortex, phylogenetically the youngest part of the brain, defines humans as a species and sexual differences in gene expression play a key role in the structural, cognitive, and functional differences between male and female cortex. It consists of six layers which are a product of complex histogenetic processes like neurogenesis and migration derived from the fetal telencephalon. Numerous gyri and sulci give it its characteristic appearance. It is divided into 52 cortical areas with specific cytoarchitecture and function accompanied by a unique set of input-output neural connections that reflect different gene expressions. The diversity of gene expression is acquired by transcriptional and epigenetic mechanisms so that only certain genes become prominent. Genes expressed in the neocortex make up about 81.8 % of the total number of protein-coding genes and its diverse expression depends on the life period, neocortical region and sex. Sexual differences arise from the joint influence of sex chromosomes and sex steroid hormones and are realized by the activity of epigenetic mechanisms and through nuclear receptors. Sexual differences in gene expression are thought to occur in all parts of the human brain and affect approximately 2.5% of the total number of expressed genes. Higher susceptibility of men and women to certain mental and neurodevelopmental disorders is also influenced by different gene expression. It is widely believed that sexual differences in gene expression affect structural, physiological and functional differences between male and female brains which are manifested by different cognitive adaptations to the similar demands of everyday life.