AIM: To assess HER-2 and p-AKT expression in upper urinary tract urothelial carcinoma (UTUC) in order to determine their value as prognostic factors of tumour progression and cancer-specific survival. PATIENTS AND METHODS: One hundred consecutive UTUC patients were retrospectively included, between 1990-2004, in 4 tissue microarrays for immunostaining. Median follow-up: 33.03 months. RESULTS: Positive HER-2 expression was found in 10 cases and cytoplasmic p-AKT expression in 84 cases; the expression intensity was strong: 30 cases, moderate: 28 and weak: 26. Nuclear p-AKT expression was found in 6 patients: 1 with strong, and 5 with moderate intensity. Nuclear p-AKT expression was an independent factor for tumour progression (HR=4.145, p=0.013), together with grade (HR=4.557, p=0.009) and stage (HR=2.085, p=0.003). In cancer-specific survival analysis, nuclear p-AKT expression (HR=4.268, p=0.017), together with grade (HR=5.214, p=0.035) and stage (HR=2.666, p=0.002) were identified as independent prognostic factors. CONCLUSION: Nuclear p-AKT expression together with stage and grade constitute independent prognostic factors for tumour progression and cancer-specific survival.