BACKGROUND: Oral cancer is a common and lethal malignancy. Direct contact between saliva and the oral cancer lesion makes measurement of tumour markers in saliva an attractive alternative to serum testing. METHODS: We tested 19 tongue cancer patients, measuring the levels of 8 salivary markers related to oxidative stress, DNA repair, carcinogenesis, metastasis and cellular proliferation and death. RESULTS: Five markers increased in cancer patients by 39-246%: carbonyls, lactate dehydrogenase, metalloproteinase-9 (MMP-9), Ki67 and Cyclin D1 (CycD1) (P< or =0.01). Three markers decreased by 16-29%: 8-oxoguanine DNA glycosylase, phosphorylated-Src and mammary serine protease inhibitor (Maspin) (P< or =0.01). Increase in salivary carbonyls was profound (by 246%, P=0.012); alterations in CycD1 (87% increase, P=0.000006) and Maspin (29% decrease, P=0.007) were especially significant. Sensitivity values of these eight analysed markers ranged from 58% to 100%; specificity values ranged from 42% to 100%. Both values were especially high for the CycD1 and Maspin markers, 100% for each value of each marker. These were also high for carbonyls, 90% and 80%, respectively, and for MMP-9, 100% and 79%, respectively. CONCLUSION: The significance of each salivary alteration is discussed. As all alterations correlated with each other, they may belong to a single carcinogenetic network. Cancer-related changes in salivary tumour markers may be used as a diagnostic tool for diagnosis, prognosis and post-operative monitoring.