Thymidylate synthase (TS, TYMS) is a 32-35kD enzyme which is coded by the TYMS gene at 18p11.32. TYMS catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) which is one of the nucleotides forming the DNA. TYMS is essential for DNA synthesis because it represents the only de novo pathway for production of thymidine and it also is the only enzyme in folate metabolism that can oxidize the 5,10-methylenetetrahydrofolate during one-carbon transfer. Therefore, TYMS is critical for regulating the supply of all 4 DNA precursors for DNA replication. In-vitro studies have shown that upregulation of TYMS is sufficient to transform immortalized mammalian cells to a malignant phenotype. TYMS is an important target for several chemotherapeutic drugs including 5-fluorouracil (5-FU). It has been suggested that tumors with low-levels of TYMS may show to a better response to 5-FU than those with high-level expression. In normal tissues, TYMS expression is ubiquitous but too low for detection by immunohistochemistry in most tissues. TYMS expression is highest in thymus, bone marrow, tonsil, lymph nodes and the testis. Among cancers, TYMS expression is highly variable between individual tumors. At least in a fraction of tumors, high TYMS expression occurs in a broad range of different tumor entities.