Evolution of the mammalian neocortex is difficult to examine directly. For this reason, comparative studies and developmental studies are the best way of gaining insight into the evolutionary process. Comparative studies indicate that neocortical evolution is constrained, and that the types of systems-level modifications made to the neocortex are limited. Developmental studies of gene expression suggest that genetic contingencies set up aspects of cortical organization and connectivity, and that the complex spatial and temporal interactions of genes constrain development and evolution. Although genes obviously contribute to phenotypic variability, variability can also be achieved through alterations in the sensory receptor arrays, or changes in sensory driven activity. The intracellular mechanisms that enable phenotypic variability might evolve, but often the phenotypic characteristic in question is context-dependent.