Aims: Ductal carcinoma in situ (DCIS) is regarded to be a non-obligate pre-invasive precursor of invasive ductal carcinoma. Some DCIS present with a periductal inflammatory infiltrate in the stroma, but the etiology of this stromal inflammatory response is currently unclear. Rab27B is a small GTPase that is involved in the release of exosomes, i.e. small intraluminal vesicles that are released upon fusion of multivesicular endosomes with the plasma membrane. Rab27B is upregulated in invasive ductal carcinoma, but its role in early breast cancer progression and the tumor immune microenvironment is still relatively unexplored. Therefore we aimed to investigate Rab27B expression in DCIS, as well as its relation with stromal inflammation. Methods: Histopathological features were analyzed in a cohort of 71 DCIS patients. Immunohistochemistry was performed on whole mount slides to assess hormone receptor status and Rab27B expression. HER2 amplification status was determined by dual-probe fluorescence in situ hybridization (FISH). Multivariate logistic regression analysis was performed to analyze which features were associated with stromal inflammation. Results: Thirty-five (49%) DCIS presented no or mild stromal inflammation, and 36 (51%) showed moderate to extensive inflammation in the periductal stroma. In multivariate analysis, high nuclear grade (p = 0.005), HER2 amplification (p = 0.002) and high Rab27B expression (p = 0.007) were independently associated with the presence of moderate to extensive stromal inflammation in DCIS. Future research should focus on the precise characterization of the stromal inflammatory infiltrate in DCIS, and explore the mechanisms by which this immune response is evoked. Disclosure: All authors have declared no conflicts of interest.