The studies of breast cancer heavily rely on the availability of experimental animal models. An ideal model of breast cancer is not only required to mimic the whole processes of tumor progress and metastasis, but also required to provide a normal human mammary microenvironment for the breast cancer cells to proliferate and metastasize. Numerous mouse models have been introduced in the literature but failed to achieve the two requirements simultaneously. In this study, we developed a novel human breast tissue-derived orthotopic and metastatic (BOM) mouse model of breast cancer, in which the normal human breast tissues were implanted subcutaneously to create a normal human mammary microenvironment, after which the human breast cancer cells were inoculated into the implants. The BOM model not only mimicked the whole processes of tumor progress and metastasis, but also allowed the orthotopic human breast cancer cells to proliferate in the normal human mammary microenvironment, and finally metastasize preferentially to the distant human tissues. Consequently, the BOM model contributed to the orthotopic tumor formation of 100% (11/11) and the metastatic tumor formation of 72.7% (8/11).