BACKGROUND: We previously identified estrogen-responsive finger protein (Efp) as an estrogen-induced gene, and showed that the positive immunoreactivity of Efp is a poor prognostic factor for patients with breast cancer. We also demonstrated that Efp has distinctive roles in innate immunity by activating pattern recognition receptor retinoic acid-inducible gene I (RIG-I). The clinical value of RIG-I protein expression in breast cancer had not been evaluated in relationship with patients' prognosis. PATIENTS AND METHODS: Tissue samples of estrogen receptor-positive invasive breast cancer were obtained from 145 female patients with breast cancer who underwent surgical treatment. Immunoreactivities of RIG-I and Efp were analyzed with the antibodies generated for the present study. RESULTS: Positive immunoreactivity of RIG-I was correlated with lower disease-free survival (P = .032) and was an independent poor prognostic factor (P = .043). RIG-I immunoreactivity was positively correlated with that of Efp (P = .0004). Patients with positive immunoreactivities of both RIG-I and Efp proteins were associated with a lower disease-free survival rate (P = .005). CONCLUSIONS: Positive immunoreactivity of RIG-I has clinical significance as a poor prognostic factor in patients with estrogen receptor-positive breast cancer. A positive correlation of RIG-I and Efp immunoreactivities was observed, and the combination of their immunoreactivities can be used to predict patients' prognosis.