The TAL-1/SCL and LYL-1 genes encode two closely related basic helix-loop-helix transcription factors involved in child T-acute lymphoblastic leukemia through chromosomal rearrangements and transcriptional deregulation. During ontogeny, Tal-1/SCL is required for hematopoietic cell generation, both in the yolk sac, where erythro-myeloid cells are first produced, then in the intra-embryonic compartment, where hematopoietic stem cells independently arise. We describe here the expression pattern of lyl-1 in mouse embryos from 7 to 14 days post coitus using in situ hybridization, as well as beta-Galactosidase (beta-Gal) expression in lyl-1-lacZ knock-in embryos, which express a C-terminally truncated Lyl-1 protein fused to the beta-Galactosidase (Lyl-1Delta/beta-Gal). In addition, we compare lyl-1 expression pattern with that of tal-1/scl. Similar to Tal-1/SCL, Lyl-1 mRNA expression occurs in the developing cardiovascular and hematopoietic systems. However, contrary to tal-1/scl, lyl-1 is not expressed in the developing nervous system. In lyl-1-lacZ knock-in heterozygous and homozygous embryos, beta-Gal expression completely correlates with Lyl-1 mRNA expression in the intra-embryonic compartment and is present: (1) in the developing hematopoietic system, precisely where hematopoietic stem cells emerge, and thereafter in the fetal liver; (2) in the developing vascular system; and (3) in the endocardium. In contrast, whereas Lyl-1 mRNA is expressed in yolk sac-derived endothelial and hematopoietic cells, Lyl-1Delta/beta-Gal is either absent or poorly expressed in these cell types, thus differing from Tal-1/SCL, which is highly expressed there at both mRNA and protein levels.