Background: The expression of trophoblastic cell surface protein 2 (Trop2) has been correlated with aggressive behavior in multiple malignant neoplasms. Moreover, it is a promising therapeutic target for several malignancies. However, data on the prognostic significance of Trop2 in breast cancer is insufficient. The current work aimed to study the prognostic significance of Trop2 expression in breast cancer and its correlation with microvascular density (MVD). Patients and Methods: Immunohistochemical expression of Trop2 was assessed in 70 cases of breast cancer and its relation to clinicopathological parameters, MVD (as assessed by CD34 immunostaining) and patient's survival was evaluated. Results: High Trop2 expression was detected in 44 cases (62.9%) of the studied cases. The expression of Trop2 was significantly related to tumor size, lymph node stage, lymphovascular invasion, tumor grade and high Ki67 index (P<0.05).   Moreover, the expression of Trop2 was significantly higher in triple-negative breast carcinoma (TNBC) than other molecular subtypes (P=0.015). Additionally, Trop2 expression was significantly correlated to MVD (r= 0.845). Both overall survival and disease-free survival were significantly shorter in the high Trop2 group than low Trop2 group (P=0.008, 0.021), respectively.  Conclusion: Trop2 can be considered as a poor prognostic marker and potential therapeutic target for breast cancer, mainly the triple-negative subtype. Since Trop2 expression was significantly correlated to MVD, we speculate that enhancement of angiogenesis could be one of the mechanisms involved in Trop2 induced tumor invasion and metastasis.