Urine cytology is the most commonly used non-invasive test for the detection of urothelial cell carcinoma (UCC). While particularly valuable for the diagnosis of high-grade tumors, its clinical usefulness is often compromised by its reduced ability to detect low-grade tumors. This low sensitivity, estimated at around 17%, is mainly explained by the lack of significant differences between the cytomorphological features of lowgrade cancer cells and benign reactive conditions. Since 70% of non-muscle invasive bladder cancers are of low-grade, there is a real quest for a complementary urinary marker able to provide adjunctive non-cytomorphological information for the more accurate detection of low-grade urothelial carcinoma in urine specimens.