Differentiation-related gene-1, DRG1, is a metastasis suppressor gene whose expression has been shown to be dysregulated in a number of malignancies. The current study examines the expression of DRG1 in a clinical breast cohort and its association with a number of clinical pathological factors using quantitative polymerase chain reaction. Additionally, DRG1 expression is targeted in vitro using ribozyme transgene technology to explore the function of DRG1 in two human breast cancer cell lines. Low levels of DRG1 were found in patients who developed metastasis (p = 0.036) and who died of breast cancer (p = 0.0048) compared to disease free patients. Knockdown of DRG1 also resulted in significantly increased invasion and motility, but decreased matrix-adhesion in MCF7 cells. Knockdown of DRG1 seemed to have minimal impact on the cellular functions of the MDA-MB-231 breast cancer cell line causing no significant differences in cell growth, invasion, motility or matrix-adhesion. Thus, DRG1 appears to be linked to development of metastasis and death in patients who died as a result of breast cancer and may be useful as a prognostic factor as its knockdown appears to be linked with increased invasion and motility and decreased adhesion in MCF7 breast cancer cells.