Background: Urine Exfoliated Cells (UEC) is the most widely used sample for noninvasive bladder cancer detection. However, current UEC-based methods including urinary cytology and other molecular detections showed low sensitivities especially for low-grade cancer (< 50% sensitivity). Epigenetic alterations such as elevated allelic expression of imprinted genes usually occur at early stages of malignancy, and can be considered as potential bladder cancer biomarkers. In this study, Quantitative Chromogenic Imprinting Gene In-Situ Hybridization (QCIGISH) was conducted to analyze the biallelic expression (BAE) and multiallelic expression (MAE) in UEC, and develop a more accurate method for early stage bladder cancer. Methods: 53 patients with urinary system diseases including 13 low-grade bladder cancer, 24 high-grade bladder cancer and 16 benign lesions, as well as 28 healthy volunteers were recruited in clinical trial NCT03563443 for validation. The total expression (TE), BAE and MAE of imprinted genes GNAS, PEG10, GRB10, SNRPN and HM13 were blindly detected by QCIGISH. The severity of malignancy was predicted by a grading model previously established on 229 tissue FFPE and cystoscopic biopsy samples, and subsequently validated with the pathology and clinical diagnosis results. Results: The QCIGISH method achieved 84.6% and 95.8% sensitivities for low- and high-grade bladder cancers, respectively, with an equally high specificity of 97.7%. The sensitivity of QCIGISH for low-grade bladder cancer is much higher than standard urinary cytology (16%), and FDA-approved molecular tests such as Hemoglobin Dipstick (38%), BTA Stat (36%), NMP22 BladderChek (25%), and ImmunoCyt (47%). Conclusions: The high accuracy of QCIGISH especially for low-grade bladder cancer demonstrated its great potential in becoming an important and powerful clinical tool for noninvasive diagnosis and large-scale screening for early bladder cancer.