Objective: Transitional cell carcinoma (TCC) of the urinary bladder is the second common cancer of the genitourinary tract. Several parameters such as clinical and pathological parameters, molecular factors, and etc play a role in determination of prognosis and type of treatment. In this research study, the relationship between grade and MDM2 oncoprotein overexpression in TCC of bladder was evaluated. Material and Methods: This cross-sectional study was carried out on 75 paraffinembedded tissue blocks (deposited in Pathology Department) from patients with TCC of urinary bladder from 2002 to 2005. In this respect, 3 μm sections were taken from each block. In one of the sections, grade of tumor was determined according to WHO/ISUP criteria using hematoxylin-eosin staining method. In another section, percent of MDM2 positive cells were determined by microscopic observation of 100 cells in each section using immunohistochemical technique and specific antibody. Results: Mean of MDM2 positive cells was %9.08 ± 4.7. In addition, mean of MDM2 positive cells in low malignant potential tissue (grade I), low grade tissue (grade II), and high grade tissue (grade III) was %3.6 ± 2.2, %8.2 ±3.5, and %13.1 ± 3.4 respectively. Meanwhile, a significant relationship was found out between grade and overexpression of MDM2 oncoprotein (p = 0.012). Conclusion: Overexpression of MDM2 oncoprotein exhibits a direct relationship with grade of TCC of the urinary bladder. The obtained results were consistent with the most previous studies. Therefore, through performing studies with a greater follow-up and entailing a larger population of patients, overexpression of MDM2 oncoprotein could be used as a prognostic parameter in TCC of urinary bladder.