Distinguishing between invasive urothelial carcinoma (UC) from other genitourinary malignancies, such as prostatic and renal carcinomas, can be difficult. Several new markers such as GATA binding protein 3 (GATA-3), S100P, and uroplakin III have been developed for this differentiation (1-7). More recently uroplakin II has been introduced (1-7). GATA-3 is a transcription factor and belongs to a distinct family of tumor suppressor genes. It is involved in human cancer cell growth and differentiation, and plays an important role in cell proliferation and apoptosis. Recent studies have found GATA-3 to be a sensitive and specific marker for UC. The level of GATA-3 expression was seen to be an independent factor predicting cancer recurrence (6,7). Uroplakins are markers of terminally differentiated bladder urothelia. Uroplakin II (UPII) is a newly described sensitive marker for UC (1-5). UPII has been shown to be a more sensitive immunohistochemical (IHC) marker than uroplakin III in UC (1,2). UPII has also been used in the diagnosis for UC using a panel that includes GATA-3 and p40 (4,5). The combination of GATA-3 (nuclear) and UPII (cytoplasmic/membrane) in a single color format increased both specificity and sensitivity in a single section (4,5). UPII has been shown to be virtually 100% specific for UC (1-3). GATA-3 increases the overall specificity when compared to UPII alone and it does not stain prostate adenocarcinoma or renal cell carcinoma (4,5). Thus, two antigens, GATA-3 (nuclear) and UPII (cytoplasmic/membrane), can be recognized and displayed on the same section by a single color format.