Background: Despite the risk of being upgraded, most DCIS remain as an indolent lesion without developing invasive disease. Therefore, it is important to stratify DCIS patients into different upgrading risk groups and to guide precise therapeutic decisions. This study aims to understand the prevalence of DCIS upgrading, and to investigate clinicopathological features that correlate with the risk of DCIS upgrading. Besides, the status of hormonal receptors (ER and PR) and HER2 are compared in both DCIS and the upgraded invasive counterparts. Materials and Methods: We collected 575 patients with a diagnosis of DCIS on biopsies, and followed up their final diagnosis on excision as well as the status of axillary lymph node involvement. Several clinicopathological factors were analyzed by both univariate and multivariate analysis to understand the risk factors associated with DCIS upgrading. The status of ER, PR, and HER2 were also compared between DCIS and their upgraded invasive counterparts. Results: The overall upgrading risk for DCIS was 19.1%, and factors associated with higher upgrade risk on multivariate analysis include ultrasound-guided biopsy (pConclusion: Suspicious microinvasion on biopsy was the only pathological parameter that was significantly associated with DCIS upgrade on excision. Other clinical parameters associated with DCIS upgrade included ultrasound-guided biopsy and left laterality of the lesion. Besides, DCIS with different ER/PR status showed distinctive HER2 status in their invasive counterparts, and ER+/PR- DCIS was most likely to develop HER2-amplified invasive carcinoma. However, most of the ER/PR status were consistent between DCIS and invasive counterparts. DCIS generally had a low risk of developing axillary lymph node metastasis, but the risk was significantly increased for upgraded cases with invasive carcinoma other than microinvasion. Finally, microinvasive carcinoma was more likely to be ER-/PR- and triple-negative, and had a significantly higher chance of HER2 amplification. Citation Format: Mingfei Yan, Phillip Bomeisl, Hannah Gilmore, Aparna Harbhajanka. Clinicopathological follow-up of breast ductal carcinoma in situ diagnosed on biopsies: A single institutional study of 575 patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-42.