The aim of this study was to analyse prognostic factors for time to treatment failure (TTF) and overall survival (OS) in patients with unresectable cancer of the pharynx. A twice daily (b.i.d.) radiotherapy with concomitant cisplatin-5-fluorouracil chemotherapy was administered to 77 consecutive patients (68 males, 9 females; median age: 56 years). The studied factors were: age, gender, tumour differentiation, tumour volume, initial hemoglobin level, karnofsky index (KI), primary tumour location, T, N, epidermal growth factor receptor (EGFR) level in the tumour (fmol/mg protein). KI and EGFR level were significant predictors in a multivariate analysis for TTF (P=0.004 and P=0.0001) and OS (P=0.004 and P=0.0001). In order to select subgroups with different outcomes, a stratification of patients was performed based on the EGFR value: patients with tumour EGFR levels <35 fmol/mg protein, between 35 and 275 fmol/mg protein and >275 fmol/mg protein had 95%, 51% and 16% 3 year OS rates, respectively (log rank test; P=0.0001). Interestingly, for patients exhibiting a complete response (CR) after concomitant b.i.d. chemo-radiotherapy, patients with EGFR levels <35 fmol/mg protein were all alive at 3 years; in contrast, there was only 70 and 13% 3 year survival rates for patients with EGFR tumour levels between 35 and 275 fmol/mg protein and above 275 fmol/mg protein, respectively. EGFR determination appears to be a powerful prognostic parameter in unresectable pharyngeal cancer patients treated by concomitant chemo-radiotherapy.