The authors assessed proliferating cell nuclear antigen (PCNA), p-53 oncoprotein and morphologic tumor front grading (TFG) in patients with advanced squamous cell carcinoma (SCC), of the larynx and a poor prognosis and tried to find a correlation with tumor stage, the Broders grading system, local and neck lymph node metastases, as well as nodal and local recurrences. In addition, utility of the parameters investigated was evaluated in developing a prognostic factor model, using uni- and multivariate Cox regression analysis. Included in this study were 54 patients (mean age 57 years +/- 8.6). PCNA-positive staining was found in all but one patient with advanced disease, while p-53 stained positively in only 24 subjects (44.4%). The PCNA index ranged from 4.6 to 59.0% (mean, 23.4 +/- 11. 0) and the p-53 index varied from 4.0 to 42.0% (mean, 17.2 +/- 8.6). The TFG score ranged from 9 to 23 points (mean, 15.1 +/- 3.2). PCNA, p-53 and TFG were found to be the markers that provided significant additional information about the biological behavior of tumor cells. The high variability of the results (PCNA, p-53) and high percentage of negatively stained cells (p-53) reduced their application in clinical use. PCNA correlated with tumor grade, G (r = 0.38; P < 0. 01), but negatively with nodal (N) disease(r = -0.37; P < 0.01). The mean values of PCNA and p-53 index were higher in the subgroup with local recurrences. Our present attempt to develop a useful prognostic factor model failed.