Transgenic (TG) mice expressing human chorionic gonadotropin -subunit (hCG) under the ubiquitin C promoter, presenting with a moderately elevated level of LH/hCG bioactivity develop multiple neoplasms secondary to the endocrine abnormalities, including mammary gland tumors after the age of 9 months. The increased levels of circulating estradiol, progesterone and prolactin of the TG females after puberty boost the lobuloalveolar development in the mammary gland resulting ultimately in the formation of estrogen and progesterone receptor negative, malignant tumors. These tumors have a similar histopathology with those observed in TG mice with activated wnt/-catenin pathway, showing increased expression of -catenin, also a common finding also in human breast tumors. Transdifferentiation is observed in mammary tumors of the hCG TG mice, accompanied by abnormal expression of the Wnt genes in the tumorous and non-tumorous mammary gland tissue. Specifically, we found increased expression of Wnt5b in the TG mammary glands at the age of 3 months, and upregulation of Wnt7b and 5b in the subsequently appearing tumors. Importantly, hCG was found to upregulate these wnt ligands in mouse mammary gland, independent of the changes in ovarian steroidogenesis. Thus, the hCG overexpressing TG mice represent a novel model that links enhanced hCG action to dysregulated wnt-signalling in the mammary gland resulting in -catenin stabilizing mammary tumorigenesis. The novel finding of hCG upregulating wnt7b and wnt5b could contribute to pregnancy induced breast cancer in humans.