The tumor suppressor gene p53 encodes for an important cell cycle regulatory protein. Loss of the protein's function is probably important for the development of a variety of malignant diseases, including oral cancer. Up to present knowledge, the mutations of the p53 gene are one of the most frequent genetic alterations detectable in human cancer. The aim of this study was to explore the capability of molecular diagnostics to identify p53 mutations (exon 5-8) in smears of the oral mucosa (polymerase chain reaction, temperature gradient gel electrophoresis). Thirty two patients with oral squamous cell carcinoma comprised the study. Biopsies of the tumor, smears of the ulcer, and smears of apparently healthy mucosa were collected from these cancer patients. Smears of 35 healthy volunteers served as controls. P53-mutations were detected in 14 of the 32 cancer patients (44%). The same mutations was also detected in the biopsy in all cases. In addition, swabs of apparently normal mucosa harboured p53-mutated cells in 4 of these 14 patients. No mutation was found in healthy volunteers. Our investigation showed the suitability of swabs for gaining sufficient material to detect p53 gene mutations in oral squamous cell carcinoma.