Background: Carcinoma of the bladder is responsible for a large percentage ofmortality due to cancer worldwide. In Egypt, it is the commonest malignancy affectingmen. Early diagnosis of bladder cancer could detect small tumor at early stage. Severalurinary markers for transitional cell carcinoma have been investigated. The United StatesFood and Drug Administration have approved nuclear matrix protein (NMP 22) for thedetection of occult or rapidly recurring disease after transurethral resection of bladdertumor.Objective: This study was designed to determine the clinical usefulness of theNuclear Matrix Protein 22 Test for the detection and follow up of patients with bladdercancer with the prognostic pathological parameters (stage and grade).Methods: One hundred fifty-six patients suffering from or being suspicious forbladder cancer and 33 healthy controls participated in a prospective clinical study.Freshly voided spot urine samples were taken for cytological examination anddetermination of NMP 22-levels by enzyme-linked immunoassay. Patients werediagnosed by TUR-Biopsy and histopathological examination.Results: Sensitivity for NMP22 test was 79% and 97% for patients with superficialbladder tumor and invasive bladder tumor respectively. While, the sensitivity for voidedurine cytology was 56% and 85% for patients with superficial bladder tumor and invasivebladder tumor respectively. Sensitivity for the NMP 22 Test according to the tumorgrading for patients with superficial bladder tumor was (results of cytology inparentheses): GI 61.5% (30.8%), G2 86.7% (66.7%), and G3 100.0% (83.3%). Sensitivityaccording to stage was 62.5% (25%) and 82.6% (60.9%) for Ta and T1 tumorrespectively. Specificity was 90.7% (96%). Receiver-operating characteristics curveinterpretation determined that 11.2 U/ml was an optimal reference value for NMP22 todetect transitional cell carcinoma of the bladder in this patient group. Comparative resultsdemonstrate a clear superiority of NMP22 over cytology in sensitivity in bladder cancerdetection (p < 0.05). Combined sensitivity of voided urine cytology with NMP22 washigher than either test alone. Sensitivity of the NMP 22 Test for patients with bladdertumor recurrence was (results of cytology in parentheses) 92.9%(50%),and specificitywas 75.0%(93.8%).Conclusions: NMP 22 is a reliable tool for detecting invasive and superficialbladder cancer. NMP 22 test results showed sufficient sensitivity in comparison withurine cytology for the detection and follow up of transitional cell carcinoma. UrinaryNMP 22 levels were significantly correlated with tumor grade The higher sensitivities ofmarkers in bilharzial than nonbilharzial bladder cancer highlight their clinical use inscreening patients with urinary bilharziasis.