Several gene expression experiments on autism spectrum disorders have been conducted using both blood and brain tissue. Individually, these studies have advanced our understanding of the molecular systems involved in the molecular pathology of autism and have formed the bases of ongoing work to build autism biomarkers. In this study, we conducted an integrated systems biology analysis of 9 independent gene expression experiments covering 657 autism, 9 mental retardation and developmental delay and 566 control samples to determine if a common signature exists and to test whether regulatory patterns in the brain relevant to autism can also be detected in blood. We constructed a matrix of differentially expressed genes from these experiments and used a Jaccard coefficient to create a gene-based phylogeny, validated by bootstrap. As expected, experiments and tissue types clustered together with high statistical confidence. However, we discovered a statistically significant subgrouping of 3 blood and 2 brain data sets from 3 different experiments rooted by a highly correlated regulatory pattern of 66 genes. This Root 66 appeared to be non-random and of potential etiologic relevance to autism, given their enriched roles in neurological processes key for normal brain growth and function, learning and memory, neurodegeneration, social behavior and cognition. Our results suggest that there is a detectable autism signature in the blood that may be a molecular echo of autism-related dysregulation in the brain.