The Wnt signal transduction pathway has been implicated in mammary tumorigenesis in the mouse. β-catenin, a key downstream effector of this pathway interacts with and thus activates the Tcf/Lef family of transcription factors. Elevated levels of β-catenin have been found in many human tumors, notably colon carcinomas. Recently, elevated levels of β-catenin have been associated with poor prognosis in human adenocarcinoma of the breast. In order to assess the possible role of β-catenin in mammary carcinoma, we have created transgenic mice bearing the MMTV–LTR driving an activated form of β-catenin. These mice develop mammary gland hyperplasia and mammary adenocarcinoma, a phenotype very similar to that of transgenic mice expressing an MMTV-driven Wnt gene. Indeed, the histopathology of the mammary tumors in Wnt-mediated adenocarcinoma is identical to that observed in our β-catenin-mediated disease model. Furthermore, putative β-catenin transcriptional targets, cyclin D1 and c-myc, are elevated in β-catenin-mediated mammary tumors and cell lines. These observations support the notion that the oncogenic Wnt pathway operates via β-catenin and its targets in the context of mammary hyperplasia and carcinoma.