Head and neck cancer arises and progresses through specific genetic alterations which lead to an invasive immortal phenotype. The process of immortalization is associated with the activation of the enzyme telomerase, a ribonucleoprotein with reverse transcriptase activity which is capable of synthesizing telomeric repeats at the end of chromosomes. This enzyme is expressed in nearly all neoplasms and germline cells and is absent in most normal human somatic cells. Because of this expression pattern testing for telomerase activity may deliver useful diagnostic and/or prognostic information about clinical tumour behaviour. Telomerase activity was therefore analysed in 16 primary lesions of head and neck squamous cell carcinomas (HNSCC) using the polymerase chain reaction-based telomeric repeat amplification protocol (TRAP). For a sensitive semiquantitative analysis of telomerase activity TRAP products were mixed with Pico Green I and the fluorescence emission intensities were measured. All 16 samples tested positive. When the Pico Green I data were compared with clinical parameters, it was obvious that N0 necks revealed significantly (p < 0.05) lower emission intensities (i.e. telomerase activity) than N + necks. Our results indicate that a high telomerase activity in HNSCC may facilitate lymph node metastasis and that the estimation of telomerase activity is a useful diagnostic tool which could influence treatment modalities.