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Abstract Urinary bladder cancer (UBC) is the most common malignancy involving the urinary system and the ninth most common malignancy worldwide. In USA, it is the most common urinary tract malignancy and the fourth most common cancer in men and 12th in women. In Egypt, It comprises 88. 3% of the total urinary system tumors according to the National cancer institute registry 2016. The expected new cases are about 10. 709 by 2020, 12. 762 by 2025 and 28. 337 by 2050. The aim of this study was to evaluate the immunohistochemical expression of TROP2, Cyclin D1 and FOXP3 in UBC and to correlate their expression with the established clinicopathological parameters and overall survival. Using the standard IHC technique, we assessed TROP2, Cyclin D1 and FOXP3 expressions in 80 bladder carcinoma cases and 20 non neoplastic bladder tissue (control group). The 80 primary bladder carcinoma cases including; 50 radical cystectomies (muscle invasive urinary bladder carcinoma) and 30 cold cup biopsies (Non muscle invasive urinary bladder carcinoma). The cases were retrieved from the archives of Pathology Department, Faculty of Medicine, Menoufia University spanning the period between December 2017 and December 2019. In the present study, the age of the patients ranged from 26 to 96 years old with a mean±SD of 63. 5±10. 3 with a median age of 65 years. 82. 5% cases were males, while 17. 5% were females. The size of tumor in the studied cases ranged from 3-9 cm, with a mean±SD of 4. 7±1. 2 and a median of 4. 7. Regarding the histologic type, 95% cases were infiltrating urothelial carcinoma and 5% cases were of Non-invasive papillary urothelial carcinoma of bladder carcinoma and according to the grade of infiltrating urothelial carcinoma, 22. 5% were of low grade and 77. 5% were of high grade. Regarding TNM staging; 37. 5% were of an early stage (Ta, T1), 62. 5% were of an advanced stage (T2, 3, 4), and 60% had LN invasion (N1, 2). Regarding the muscularis propria invasion, 62. 5% were muscle invasive urinary bladder carcinoma (MIUBC), while 37. 5% were non- muscle invasive urinary bladder carcinoma (NMIUBC). Trophoblastic cell surface antigen (TROP-2) was first identified as a cell surface marker for trophoblast cells. The gene that codes for TROP-2 is called, tumor-associated calcium signal transducer 2 (Tacstd2), that is found on chromosome 1p 32. TROP-2 was subsequently reported to be over-expressed in a variety of human carcinomas and its overexpression is associated with tumor aggressiveness and poor prognosis. Regarding TROP2 expression, TROP2 was expressed in 85% of non neoplastic bladder tissue (control group) and in 97. 5% of UBC cases without significant difference (p=>0. 05). In the present study, TROP2 higher percent (P=0. 001), diffuse pattern (P=0. 001), and predominant strong (P=0. 001), High IRS (P=0. 001) and higher H score of TROP2 (P=0. 001) were in favor of MIUBC in comparison with NMIUBC. Moreover, TROP2 high immunoreactive score (IRS), predominant strong intensity and diffuse pattern of TROP2 expression were statistically associated with |