Squamous differentiation occurs in up to 20% of urothelial carcinoma cases and is thought to be an unfavorable prognostic factor. Data from urothelial carcinoma in patients treated with cystectomy from 2002 to 2014 at Roswell Park Cancer Institute were retrospectively reviewed. A 2-tier system was adopted for stage analysis. T1 and T2 disease were grouped in organ-confined and low-stage categories, whereas T3 and T4 disease were grouped in high-stage categories. The extent of squamous differentiation was semi-quantified as focal (≤20%) or extensive (> 20%). Squamous differentiation occurred in 19.3% (47 of 244) of cases. Urothelial carcinoma with squamous differentiation presented with a significantly higher rate of high-stage disease compared with pure urothelial carcinoma (72.3% vs 43.1%; P < .01). The nodal metastatic rate in urothelial carcinoma with extensive squamous differentiation was significantly higher than that seen in pure urothelial carcinoma (46.2% vs 27.0%; P = .04). Urothelial carcinoma with squamous differentiation is associated with advanced tumor stage. In addition, urothelial carcinoma with extensive squamous differentiation presented with a significantly higher rate of nodal metastasis. These findings can be the contributing factors for the unfavorable clinical outcomes seen in patients with urothelial carcinoma and squamous differentiation.