There are a wide variety of tumor markers now available that proved to be of value in the management of cancer patients. Of these markers, tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS) are well known in the field of bladder cancer. TPA was found to be a mixture of cytokeratins 8, 18 and 19 and recent investigations proved that TPS is keratin 18. The aim of the present study was to assess the clinical value of urinary cytokeratin 19 (CYFRA21-1) in the differential diagnosis between bladder cancer and benign urinary tract diseases represented by bilharziasis. Two hundreds and seventy individuals were included in the present study: 186 with bladder cancer representing the different stages and grades, 44 with urinary tract bilharziasis and 40 normal healthy controls. CYFRA21-1 was evaluated in 24-hour urine samples by ELISA using the automatic set supplied by Boehringer Manheim, Manheim, Germany (ES 300). Results of this study revealed significant elevation of CYFRA21-1 in bladder cancer followed by bilharziasis. 82.3% (153/186) of bladder cancer patients and 11.4% (5/44) of bilharzial patients exhibited CYFRA21-1 levels above the upper limit of the control group (3 micrograms/24-hr). CYFRA21-1 was more sensitive in advanced than early stages of bladder cancer and in patients with positive than those with negative lymph nodes, but association of tumor with bilharziasis did not markedly affect its level.