BACKGROUND Over-expression of human epidermal growth factor receptor (EGFR) is associated with a variety of human malignancies, including head and neck cancer. It has also been studied for its effect on cancer cell responses to chemotherapy. To accurately measure changes in EGFR expression that might be of diagnostic or prognostic importance in head and neck cancers, a quantitative assay for the direct detection of EGFR messenger ribonucleic acid (mRNA) was developed. METHODS Our method was based on competitive reverse transcriptase-polymerase chain reaction (RT-PCR) that was able to measure EGFR mRNA levels undetectable by northern-blot analysis. We measured EGFR mRNA by RT-PCR in human head and neck cancers and their corresponding adjacent, histologically normal tissues and in cisplatin-treated and untreated oral epithelial cell lines. RESULTS All the tumor samples had higher EGFR mRNA levels than their corresponding adjacent normal tissues. It is also shown that EGFR mRNA levels in normal oral epithelial cells were elevated after exposure to cisplatin. In contrast, EGFR mRNA levels in oral cancer cells were decreased after the exposure, suggesting that increased EGFR expression may have different functions in cancer cells and in normal cells under stress. CONCLUSIONS Accurate monitoring of EGFR expression may be a useful marker for diagnosis, treatment, and prognosis of head and neck cancer.