CSF-1 promotes the progression of mammary tumors to malignancy. In human breast carcinomas, overexpression of CSF-1 and its receptor (CSF-1R) correlates with poor prognosis. To determine if CSF-1 is causally involved in breast cancer progression, researchers crossed a transgenic mouse susceptible to mammary cancer with mice containing a recessive null mutation in the CSF-1 gene (Csf1^op). They found that the absence of CSF-1 did not affect the incidence or growth of primary tumors but delayed their development to invasive, metastatic carcinomas. Transgenic expression of CSF-1 in the mammary epithelium of both Csf1^op/Csf1^op and wild-type tumor-prone mice accelerated tumor progression and increased pulmonary metastasis. This was associated with enhanced infiltration of macrophages into the primary tumor. These studies demonstrate that CSF-1 selectively promotes the progression of tumors to malignancy. CSF-1 may promote metastatic potential by regulating the infiltration and function of tumor-associated macrophages. The data suggest that agents targeting CSF-1/CSF-1R activity could have important therapeutic effects. The absence of CSF-1 delayed tumor progression and metastasis, while its restoration accelerated these processes. CSF-1 is expressed in macrophages but not in tumor cells, indicating that macrophages are the primary target for CSF-1 action. The findings suggest that CSF-1 plays a critical role in the progression of mammary tumors to malignancy by promoting the infiltration and function of macrophages.CSF-1 promotes the progression of mammary tumors to malignancy. In human breast carcinomas, overexpression of CSF-1 and its receptor (CSF-1R) correlates with poor prognosis. To determine if CSF-1 is causally involved in breast cancer progression, researchers crossed a transgenic mouse susceptible to mammary cancer with mice containing a recessive null mutation in the CSF-1 gene (Csf1^op). They found that the absence of CSF-1 did not affect the incidence or growth of primary tumors but delayed their development to invasive, metastatic carcinomas. Transgenic expression of CSF-1 in the mammary epithelium of both Csf1^op/Csf1^op and wild-type tumor-prone mice accelerated tumor progression and increased pulmonary metastasis. This was associated with enhanced infiltration of macrophages into the primary tumor. These studies demonstrate that CSF-1 selectively promotes the progression of tumors to malignancy. CSF-1 may promote metastatic potential by regulating the infiltration and function of tumor-associated macrophages. The data suggest that agents targeting CSF-1/CSF-1R activity could have important therapeutic effects. The absence of CSF-1 delayed tumor progression and metastasis, while its restoration accelerated these processes. CSF-1 is expressed in macrophages but not in tumor cells, indicating that macrophages are the primary target for CSF-1 action. The findings suggest that CSF-1 plays a critical role in the progression of mammary tumors to malignancy by promoting the infiltration and function of macrophages.