A series of 71 patients undergoing radical surgical resection for stage III and IV laryngeal carcinoma (LC) consecutively diagnosed was prospectively studied in order to evaluate the relative weight of p53 expression in predicting clinical outcome, All the patients taking part in this study were followed up for a median of 18 months (range: 6-41 months). Positive staining for p53 protein was detected in 44 of 71 (62%) of these tumors on paraffin-embedded tissue, even in dysplastic areas. Among the clinico-pathological and biological parameters analyzed, only flow-cytometric S-phase (FCM-S) Values of turners showed a significant relationship to p53 immunostaining (p=0.01). With Kaplan-Meier estimation, in multivariate analysis only high FCM-S (>15.1) was independently related to risk of relapse (RR=5.82), while both FCM-S and site (subglottis) were related to risk of death (RR=6.83 and RR=14.3, respectively). These findings indicate that p53 immunoreactivity, though of no utility as a prognostic indicator, probably plays a role in the early stages of LC tumorigenesis.