Glutaredoxin (Glrx) uses the reducing power of glutathione to maintain and regulate the cellular redox state. Substantial evidence indicates that the alteration of cellular redox status is a critical factor involved in cell growth and death and results in tumorigenesis. We investigated levels of expression of all Glrx genes in a variety of cancers using a real-time polymerase chain reaction (RT-PCR). Among members of the Glrx, family, Glrx3 (PICOT: PKC-interacting cousin of thioredoxin) was preferentially induced in lung (55.3+/-30.1-fold induction) and colon (50.2+/-28.8-fold induction) cancer compared to their normal tissues (lung>or=colon>breast>ovary>bladder>prostate>thyroid>lymphoma>liver>or=kidney cancers). By contrast, the magnitude of induction folds in other cancer tissues was ranged from 0.83 to 4.0. Moreover, the induction folds of Glrx3 mRNA in colon and lung cancer tissues were significantly higher when compared to those of all thioredoxin (Trx) and peroxiredoxin (Prx) members. Western blot analysis of different and paired cancer tissues revealed the consistent and preferential expression of Glrx3 in lung and colon cancers. Taken together, these results suggest that Glrx3 could take a pivotal role in colon and lung cancer cells during the tumorigenesis.