Multiple types of indirect evidence have been used to support theories of altered cortical connectivity in autism spectrum disorders (ASD). In other developmental disorders reduced spine expression is commonly found, while conditions such as fragile X syndrome show increased spine densities. Despite its relevance to theories of altered cortical connectivity, synaptic spine expression has not been systematically explored in ASD. Here we examine dendritic spines on Golgi-impregnated cortical pyramidal cells in the cortex of ASD subjects and age-matched control cases. Pyramidal cells were studied within both the superficial and deep cortical layers of frontal, temporal, and parietal lobe regions. Relative to controls, spine densities were greater in ASD subjects. In analyses restricted to the apical dendrites of pyramidal cells, greater spine densities were found predominantly within layer II of each cortical location and within layer V of the temporal lobe. High spine densities were associated with decreased brain weights and were most commonly found in ASD subjects with lower levels of cognitive functioning. Greater spine densities in ASD subjects provide structural support for recent suggestions of connectional changes within the cerebral cortex that may result in altered cortical computations.