Background: Trimodality bladder-sparing therapy has become an accepted treatment for selected patients with muscle-invasive bladder cancer (MIBC). As some of the histologic variants of urothelial carcinoma (VUC) are more resistant to chemotherapy and radiotherapy compared with pure urothelial carcinoma (PUC), it is still controversial whether bladder-sparing therapy provides comparable disease control in VUC. We have developed a tetra-modality bladder-sparing therapy consisting of maximal transurethral resection (TUR), chemoradiotherapy (CRT), and consolidative partial cystectomy, which has theoretical advantage in locoregional control by surgically eliminating chemo- and radio-resistant cells (Koga et al, Urol Oncol 2013, BJU Int 2012). Methods: After maximal TUR and CRT (40Gy + cisplatin), treatment response was evaluated by cytology, imaging and tumor-site rebiopsy. Complete responders were candidate for consolidative partial cystectomy, while radical cystectomy was recommended for others. VUC identified in maximal TUR samples were categorized according to the 2004 World Health Organization Classification. Response rate to CRT, MIBC recurrence-free survival and cancer-specific survival (CSS) were compared between patients with PUC and VUC. Results: Between 1997 and 2016, 153 consecutive patients with cT2-3N0M0 bladder cancer (median age 69, female/male = 33/120, cT2/3 = 99/54) entered tetra-modality bladder-sparing protocol. VUC was identified in 37 (24%) of the patients, including glandular in 12 (8%), squamous in 11 (7%), micropapillary in 8 (5%), sarcomatoid in 2 (1%), microcystic in 2 (1%), and lymphoepithelioma-like in 1 (0.7%). There was no difference in the response rate to CRT between PUC and VUC (71% vs 84%, p = 0.13). Among the patients with PUC (n = 75) and VUC (n = 31) who underwent partial cystectomy, 5-yr MIBC recurrence-free rates were 92% and 100% (p = 0.21), and 5-yr CSS rates were 93% and 94% (p = 0.64), respectively. Conclusions: Tetra-modality bladder-sparing therapy incorporating partial cystectomy could provide favorable locoregional control and survival for patients with VUC.