We recently characterized a genomic region located upstream of the mouse pre-T cell receptor α (pTa) gene, which controls pTa expression in pre-T cells. We now report an unexpected homology between this region and a region in the mouse X chromosome inactivation center between the 3′ end of the Xist gene and the start of an antisense transcript Tsix. The homology is extended over 4 kb of genomic sequence split by an expanded repeat region and is observed only in the mouse, not in the rat. Despite high sequence similarity to the pTa transcriptional enhancer, the homologous X chromosome fragment appears to have lost its enhancer activity. These data underscore the complex organization of the mouse genome and, in particular, of the X chromosome inactivation center.