The high rate of autism in tuberous sclerosis complex provides an opportunity to study the pathogenesis of autism. This study investigated the relationship between a DSM-IV diagnosis of autism and tuber location in a sample of 50 individuals with tuberous sclerosis complex. Chi-square analyses revealed no differences between individuals with autism (n = 15) and those without autism (n = 35) on the occurrence of tubers in the right or left frontal, occipital, parietal, or temporal regions. There were no differences between the two groups in the occurrence of tubers in subcortical or cortical regions. In the largest sample to date, these results fail to support the hypothesis that supratentorial tuber location is a marker for autism.