In this study we investigated the incidence of mutations and loss of heterozygosity (LOH) of the TP53 gene in DNA samples from paired tumor and adjacent normal tissue from 90 patients with untreated squamous-cell carcinoma of the head and neck. Evidence for TP53 mutations were demonstrated in 53% (48/90) of the cases analyzed. All cases were also examined for loss of heterozygosity, using a PCR-based polymorphic marker at TP53. LOH was found in 36 out of 72 (50%) informative cases. Direct sequencing of PCR products was performed in 45 cases with evidence of mutations. The sequencing results revealed the presence of base-substitutions (67%), deletions (29%) and insertions (4%). Of the base-substitutions, 70% were transitions and 30% were transversions. Demographic variables, tumor site, stage (TNM), family history of cancer, lymph-node involvement and histological grade were not important predictors of TP53 mutations. Nor did TP53 genetic alterations correlate with survival status. In conclusion, we show that TP53 genetic alterations are frequent in head-and-neck tumors, but are not associated with clinicopathological variables or disease progression. Our study provides an evaluation of the spectrum of TP53 mutations in the pathogenesis of head-and-neck carcinoma in Brazil.