We present the clinicopathological features of eight cases of large cell undifferentiated bladder carcinoma not otherwise specified (LCUBC). LCUBC was characterised by sheets of large polygonal or round cells with moderate to abundant cytoplasm and distinct cell borders. The LCUBC component varied from 90 to 100% of the tumour specimen with five cases showing pure LCUBC. The architectural pattern of the tumour varied from infiltrating tumour to solid expansile nests with focal (<5%) discohesive growth pattern in two cases. Immunohistochemical staining demonstrated that LCUBC cases were positive for cytokeratins AE1/AE3 and 7; CAM 5.2, CK20, thrombomodulin and uroplakin III were positive in six, three, three and two cases, respectively. Other immunohistochemical markers performed in the differential diagnosis context included alpha-fetoprotein, beta human chorionic gonadotrophin (betahCG), prostate specific antigen (PSA), vimentin, synaptophysin and chromogranin and all were negative. Ki-67 and p53 labelling indexes were 50-90% and 40-90%, respectively. All patients had advanced stage cancer (>or=pT3) and seven (87.5%) had lymph node metastases. Follow-up information was available in all cases, with a range of 6-26 months (mean 10.6 months). Six patients died of disease between 5 and 26 months and two patients were alive with metastases at 6 and 14 months. The prognosis of LCUBC was compared with conventional urothelial carcinoma of similar stages showing survival differences (p =0.0004). In summary, LCUBC is an aggressive variant of urothelial carcinoma that presents at an advanced stage.