Recent data indicate that, similar to p63 and p73, several different p53 isoforms can be produced in humans through alternative initiation of translation, usage of an internal promoter and alternative splicing. These isoforms are reported to have varying functions and expressions. In squamous cell carcinoma of the head and neck (SCCHN), disruption of the p53 pathway is one of the most common genetic alterations. However, to our knowledge, no studies regarding the expression of different p53 isoforms in SCCHN have so far been performed. We screened for the expression of different p53 isoforms in SCCHN and clinically normal oral epithelia using nested RT-PCR. p53 mRNA was expressed in all tumours, all matched clinically normal tissue adjacent to the tumour and in buccal mucosa from healthy volunteers. Of the novel isoforms, p53beta was detected in the majority of samples analysed, and all of the recently described isoforms were also detected in at least some tumour and normal epithelium samples, with the exception of Deltap53 isoforms. We conclude that p53 variant mRNAs are expressed in both normal oral stratified epithelium and SCCHN. Improvements in methodologies and reagents to detect and quantify p53 isoform expression in clinical material will be required to correlate p53 status with clinical outcomes.