This study identifies approximately 8,000 ubiquitously expressed genes in human and mouse tissues, which account for about 75% of all mRNAs in most tissues. These genes are often intracellular and involved in metabolism, transcription, RNA processing, or translation. In contrast, genes for secreted or plasma membrane proteins are generally expressed in only a subset of tissues. The distribution of expression levels is broad but continuous, with no clear distinction between expression classes. Expression estimates that include reads mapping to coding exons only correlate better with qRT-PCR data than those including 3'UTRs. Muscle and liver have the least complex transcriptomes, expressing predominantly ubiquitous genes, while brain, kidney, and testis have more complex transcriptomes. Brain mRNAs have unusually long 3'UTRs, suggesting added complexity in UTR-based regulation. The study supports a model where variable exterior components feed into a large, densely connected core of ubiquitously expressed intracellular proteins. The results highlight the importance of core genes in maintaining cellular functions across tissues and suggest that tissue-specific differences are primarily in the expression of receptors and ligands involved in communication. The study also shows that the number of ubiquitously expressed genes is higher than previously estimated by other methods, and that transcriptome complexity varies across tissues, with brain, kidney, and testis having more complex transcriptomes. The study also finds that 3'UTR lengths vary significantly between different functional groups of genes, with longer UTRs associated with genes involved in development, morphogenesis, and signal transduction. The findings provide insights into the functional roles of genes and the regulation of gene expression in different tissues.This study identifies approximately 8,000 ubiquitously expressed genes in human and mouse tissues, which account for about 75% of all mRNAs in most tissues. These genes are often intracellular and involved in metabolism, transcription, RNA processing, or translation. In contrast, genes for secreted or plasma membrane proteins are generally expressed in only a subset of tissues. The distribution of expression levels is broad but continuous, with no clear distinction between expression classes. Expression estimates that include reads mapping to coding exons only correlate better with qRT-PCR data than those including 3'UTRs. Muscle and liver have the least complex transcriptomes, expressing predominantly ubiquitous genes, while brain, kidney, and testis have more complex transcriptomes. Brain mRNAs have unusually long 3'UTRs, suggesting added complexity in UTR-based regulation. The study supports a model where variable exterior components feed into a large, densely connected core of ubiquitously expressed intracellular proteins. The results highlight the importance of core genes in maintaining cellular functions across tissues and suggest that tissue-specific differences are primarily in the expression of receptors and ligands involved in communication. The study also shows that the number of ubiquitously expressed genes is higher than previously estimated by other methods, and that transcriptome complexity varies across tissues, with brain, kidney, and testis having more complex transcriptomes. The study also finds that 3'UTR lengths vary significantly between different functional groups of genes, with longer UTRs associated with genes involved in development, morphogenesis, and signal transduction. The findings provide insights into the functional roles of genes and the regulation of gene expression in different tissues.