Purpose A subset of patients with intermediate 21-gene signature assay recurrence score may bene t from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk.Methods Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent de nitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included.RNA was extracted from archived formalin-xed, para n-embedded samples, and 95-gene signature was calculated.Results Two hundred six patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was signi cantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coe cient r = 0.27), which might suggest that 95-gene signature re ects biological characteristics differing from what 21-gene signature shows.Conclusions The 95-gene signature strati es patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively-accrued TAILORx population is warranted to con rm that 95-gene signature can identify patients who would bene t from adjuvant chemoendocrine therapy.