The first tumor marker reported was Bence Jones protein in 1846 by precipitation of a protein in acidified boiled urine. The measurement of Bence Jones protein has been a diagnostic test for multiple myeloma. The first modern tumor marker used to detect cancer was human chorionic gonadotrophin (HCG), a marker used in pregnancy tests. High level of HCG in the blood may indicate the presence of a placental malignancy. After pregnancy if the uterus continues to enlarge; then a high level of HCG in the blood may indicate the presence of a cancer of the placenta called as Gestational trophoblastic disease. This marker is still used to help in their diagnosis & to monitor their response to therapy. The first success in developing a blood test for a common cancer was in 1965, when Carcinoembryonic antigen was found in the blood of some patients with colon cancer. By the end of 1970s several other blood tests had been developed for different cancers. Some proteins are secreted and/or cleaved into the extra cellular milieu and may represent valuable serum biomarkers for diagnostic purpose. This review is all about the various salivary tumor markers which help in diagnosis of oral squamous cell carcinoma.