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Background: Data mining from a published transcriptome of urinary bladder urothelial carcinomas (GSE32894), PTP4A3 was identified as the most significantly upregulated gene among those related to prenylated protein tyrosine phosphatase activity (GO: 0004727). We therefore analysed PTP4A3 transcript and protein expression and their clinicopathological and prognostic significance in our well-characterised cohort of urothelial carcinomas. Methods: PTP4A3 transcript level was assessed in 23 samples of urothelial carcinoma of the urinary bladder with laser capture microdissection coupled with real-time qRT-PCR. PTP4A3 protein expression was determined by immunohistochemistry and evaluated by using H-score in 296 urinary bladder urothelial carcinomas and 340 upper urinary tract urothelial carcinomas, respectively. Both transcript and protein expression statuses were further correlated with clinicopathological features and protein expression was tested for disease-specific survival (DSS) and metastasis-free survival (MeFS). Findings: PTP4A3 transcripts were markedly upregulated in deeply invasive urothelial carcinomas (p<0.001). For both urinary tract and urinary bladder urothelial carcinomas, PTP4A3 protein overexpression was significantly associated with advanced pT status (both p<0.001), nodal metastasis (both p<0.001), and vascular invasion (both p<0.001). PTP4A3 overexpression not only predicted worse DSS (both p<0.0001) and MeFS (upper urinary tract, p<0.0001; urinary bladder, p=0.0005) at univariate analysis, but also inferior DSS (upper urinary tract, p=0.001; urinary bladder, p<0.001) and MeFS (upper urinary tract, p=0.001; urinary bladder, p=0.007) in multivariate analysis. Interpretation: PTP4A3 overexpression is an independent prognosticator for urothelial carcinoma, suggesting its potential prognostic and therapeutic value in urothelial carcinoma. [ABSTRACT FROM AUTHOR]