An increasing number of genes known to be critical for cell cycle control, differentiation, and tumor suppression have been found to impact development of the placenta. To elucidate how these genes contribute to development of embryonic and extra‐embryonic lineages, we generated a transgenic mouse in which the Cre transgene is driven by placenta‐specific regulatory sequences from the human CYP19 gene. Using ROSA26 conditional reporter mice, we could detect expression of the CYP19‐Cre transgene throughout the extra‐embryonic ectoderm and in the ectoplacental cone at embryonic day 6.5 (E6.5). By E11.5, recombination of LoxP reporter sites was detected in all derivatives of trophoblast stem cells, including spongiotrophoblast, giant cells, and labyrinth trophoblasts. We conclude that the CYP19‐Cre transgenic mouse developed here can be used in combination with conditional alleles to distinguish between embryonic and extra‐embryonic gene function, and to begin to map the period of time when gene function is critical during development. genesis 45:129–134, 2007. © 2007 Wiley‐Liss, Inc.