Genes involved in embryonic development can play a major role in cancer. Hox genes encode proteins that control the expression of other genes. They occupy a key position in the genetic hierarchy dictating the formation of the embryo. In numerous tumours, expression of specific Hox genes is altered. Misregulation of Hox genes can perturb expression of effectors, causing improper activation of embryonic processes that may lead to cancer. We have produced a mutant mouse line devoid of Hoxa5 function. The Hoxa5 mutation results in defects affecting several structures, such as the mammary gland, and reveals the crucial role of Hoxa5 in embryo development. In humans, deregulated Hoxa5 expression can cause cancer: Hoxa5 upregulation is involved in leukaemogenesis, while the loss of Hoxa5 expression is linked to breast cancer. Our Hoxa5 mice do not develop spontaneous tumours, showing that this genetic lesion is not sufficient to trigger cancer. However, when combined to a mutation in the p53 gene, known as the guardian of the genome, the Hoxa5 mutation causes mammary tumours. Using our mouse model, we propose to resolve the role and the mechanisms of actions fulfilled by Hoxa5 during mammary tumorigenesis. These studies may reveal novel molecular targets for the design of effective therapy and demonstrate that Hoxa5 can serve as a valuable molecular prognostic marker in the diagnostic of breast tumours.