Objective: Expression of biomarkers and their prognostic relevance may differ between primary tumours (PT) and its metastases (MET). There is little information about this phenomenon concerning apoptosis and cellcycle associated biomarkers in urothelial bladder cancer (UCB). Method: Nodal positive patients (n=152) with UCB underwent cystectomy and lymphadenectomy. Immunohistochemical expression of bcl-2, bcl-6, MDM-2, p53 and CyclinD1 was quantified in tissue microarrays constructed from PT and corresponding nodal MET. Results: Frequency of MDM-2 positivity increased from PT (17 %) to MET (37 %, p < 0.001). This trend was not significant for bcl-2 (PT: 7 %; MET: 10 %, p=0.4) and bcl-6 (PT: 8 %; MET: 12 %, p=0.08). Median percentage of p53 and CyclinD1 immunostained cells increased significantly (p<0.05) from PT (15 %/30 %) to MET (40 %/50 %). MDM-2 and CyclinD1 expression were positively correlated in PT (p<0.004) and MET (p<0.002). p53 and MDM-2 positivity were inversely correlated in PT (p<0.03). Only high CyclinD1 expression in the metastases predicted early death significantly and independently (p=0.017). Conclusion: Biomarkers of apoptosis and cell-cycle associated are up-regulated in the metastases indicating differences in survival and proliferation of cancer cell compared to primary tumours. Both tumor components may harbor different prognostic information and are not necessarily surrogates for each other.