The selective sensitivity of non-squamous NSCLC to pemetrexed cytotoxicity is thought to be related to the levels of expression of thymidylate synthase (TS), an essential enzyme for the de novo synthesis of thymidylate and subsequently DNA synthesis, and one of the main intracellular molecular targets of pemetrexed; indeed, elevated TS expression has been proposed as a biomarker of resistance to pemetrexed-based chemotherapy[5–13]. This evidence concerns the gene TYMS and non-small cell lung carcinoma.