ABSTRACT: The 21-gene recurrence score (RS) testing could guide treatment for luminal breast cancer with the histological non-special type (NST). However, there is limited data on its role in invasive lobular carcinoma (ILC) or other special types (ST). In the current study, we retrospectively included patients with the 21-gene RS testing between Jan. 2009 and Dec. 2017 and compared the RS distribution as well as gene expression levels among NST, ILC, and other ST with favorable prognosis. Adjuvant chemotherapy usage, clinical outcomes, and decision-making change due to RS testing were also analyzed. A total of 1736 patients were included: 1511 (87.0%) patients with NST, 79 (4.6%) with ILC, and 146 (8.4%) with ST. The median RS was 25 and 25 in the NST and ILC groups, which was 22 in the ST group (P=0.001). Compared with NST, ILC had almost similar expression of the cancer-related genes, while ST had lower expression of genes involved in the proliferation group. The rate of adjuvant chemotherapy usage was 6.7%, 38.1%, and 54.5% for ILC patients, and was 7.1%, 15.8%, and 17.8% for ST patients in the low- (RS<18), intermediate- (RS18-30), and high-risk (RS>30) RS groups, both of which were lower than that for NST patients. RS was associated with chemotherapy usage in NST patients but not in ILC or ST patients by multivariant analysis. After the testing, 20.5% of patients with NST had changes in chemotherapy decision-making, which is 21.5% in ILC patients and 16.4% in ST patients (P=0.490). Furthermore, the prognostic value of RS was only observed in NST cohort but not in ILC or ST patients. In conclusion, ST had lower RS than NST and ILC, which were mainly due to the lower expression of genes in the proliferation group. The 21-gene RS results were associated with chemotherapy usage in the NST groups, while its role in ILC and ST patients deserve to be further studied.