Abstract Backgroud Since the results of TAILORx trial were published, it was shown that premenopausal young patients with intermediate Oncotype Dx(ODx) recurrence score(RS) (16-25) may benefit from adjuvant chemotherapy. In secondary analysis of the TAILORx trial, clinicopathological features can provide complementary information in addition to Oncotype Dx results. Although ambiguous benefit of adjuvant chemotherapy in premenopausal women with intermediate risk makes clinical decision difficult, the baseline characteristic may vary depending on menopausal status. This study intends to analyze whether the intermediate-risk group shows differences in characteristics by menopausal status. Materials and Methods 760 early breast cancer patients with ER positive, HER2 negative and lymph node negative patients who have been tested ODx from July 2013 to December 2020 at Severance Hospital were retrospectively reviewed. Results Of the 760 patients, 262 patients were postmenopausal status and 498 patients were premenopausal status. Among 262 postmenopausal patients, 152 patients were in low-risk group(RS 0-20), 43 patients were in intermediate-risk group(RS 21-25), 67 patients were in high-risk group(RS 26-100). Among 498 patients, 353 patients were in low-risk group(RS 0-20), 75 patients were in intermediate-risk group(RS 21-25), 70 patients were in high-risk group(RS 26-100), respectively. In premenopausal patients with intermediate risk, clinical risk group, PR score, and Ki-67 showed a significant difference from the low risk group(p-value 0.003, <0.001 and 0.005, respectively), but no significant difference from the high risk group(p-value 0.242, 0.085 and 0.729, respectively). However, in postmenopausal patients with the intermediate risk, clinical risk group and Ki-67 did not show a significant difference from the low risk group(p-value 1.000 and 0.120, respectively), but showed a significant difference from the high risk group.(p-value 0.009 and 0.001, respectively). Conclusion In this study, some of clinicopathological characteristics of premenopausal patients with intermediate risk were closer to those of high risk group than in the low risk group, unlike postmenopausal patients with intermediate risk. In premenopausal patients with intermediate risk, benefits from adjuvant chemotherapy may be unclear, but when considering the baseline characteristic itself, there is a significant difference with the low risk group when compared with postmenopausal patients. In that point of view, more aggressive treatment decision like adjuvant chemotherapy would be helpful to premenopausal patients with intermediate risk. Keywords: 21-gene recurrence score, premenopausal breast cancer, clinicopathological features Citation Format: Jung Min Park, Jee Hyun Ahn, Soon Bo Choi, Jieon Ko, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong-Woo Park, Seho Park. Distinctive clinicopathological features of premenopausal women with intermediate 21-gene recurrence score [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-13.