The ERas gene is expressed in mouse embryonic stem (ES) cells and promotes their in vitro proliferation and tumorigenicity. We analyzed the expression of the human ERas gene in human ES cells by reverse transcription-polymerase chain reaction (RT-PCR) and serial analysis of gene expression but could not detect a full-length coding transcript. Sequence analysis predicted a premature polyadenylation signal for the human ERas transcript, which we confirmed by 3' RACE analysis. By RT-PCR, we identified a truncated noncoding transcript in human ES cells that is downregulated during differentiation, suggesting conserved tissue specificity of the promoter region. Previous reports and expressed sequence tag databases indicate that orthologues of this gene are expressed in other mammals, including the mouse, dog, and cow, which suggests that it became a silenced pseudogene relatively recently in mammalian evolution. In addition to the premature polyadenylation site, both the human and chimpanzee ERas genes include typical Alu-S retrotransposon insertions that could also influence expression at this locus. The lack of ERas expression in human ES cells suggests that they could have significantly different tumorigenic properties than mouse ES cells.