Dendritic spines of pyramidal neurons are the targets of most excitatory synapses in the cerebral cortex, and dendritic spine morphology directly reflects their function. However, there are scarce data available regarding both the detailed morphology of these structures for the human cerebral cortex and the extent to which they differ in comparison with other species. Thus, in the present study, we used intracellular injections of Lucifer yellow to reconstruct-in three dimensions-the morphology of basal dendritic spines from pyramidal cells in the human and mouse CA1 hippocampal region and compared these spines with those of the human temporal and cingular cortex. We found that human hippocampal dendrites show lower spine density, larger volume, and longer length of dendritic spines than mouse CA1 spines. Furthermore, human hippocampal dendrites show higher spine density, smaller spine volume, and shorter length compared to dendritic spines from the human temporal and cingular cortex. This morphological diversity suggests an equally large variability of synaptic strength and learning rules across these brain regions in humans and between humans and mice. Nevertheless, a balance between size and density was found in all cases, which may be a cortical rule maintained across cortical areas and species.