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Expressions of human p16 and p27 were tested for correlations with clinicopathologic features of urothelial carcinoma (UC). Tissue microarrays (TMA) constructed from paraffin-embedded specimens from 78 patients with UC were analyzed by immunohistochemical staining. In 49 of the 78 tumors (63%), high p16 expression was associated with absence of tumor invasiveness and low-grade carcinoma (p = 0.003 and p = 0.046, respectively). The p27 expression was high in 33 of the 78 tumors (42%) and showed a significant negative association with invasiveness, carcinoma grade, and tumor size (p = 0.016, p = 0.046, and p = 0.014, respectively). Kaplan–Meier analysis indicated that patients with high p27 levels had longer than average overall survival (p = 0.021). This study demonstrates that p16 and p27 are prognostic indicators of tumor stage and grade in UC and that they provide clinicians with the ancillary information needed for selecting suitable therapeutic strategies.