The objectives of this study were to examine serum periplakin expression in patients with urothelial carcinomaof the urinary bladder and in normal controls, and to examine relationships with clinicopathological findings.Detection of serum periplakin was performed in 50 patients and 30 normal controls with anti-periplakinantibodies using the automatic dot blot system, and a micro-dot blot array with a 256 solid-pin system. Levelsin patients with urothelial carcinoma of the urinary bladder were significantly lower than those in normalcontrols (0.31 and 5.68, respectively; p<0.0001). The area under the receiver-operator curve level for urothelialcarcinoma of the urinary bladder was 0.845. The sensitivity and specificity, using a cut-off point of 4.045, were83.7% and 73.3%, respectively. In addition, serum periplakin levels were significantly higher in patients withmuscle-invasive cancer than in those with nonmuscle-invasive cancer (P = 0.03). In multivariate Cox proportionalhazards regression analysis, none of the clinicopathological factors was associated with an increased risk forprogression and cancer-specific survival. Examination of the serum periplakin level may play a role as a noninvasivediagnostic modality to aid urine cytology and cystoscopy.