Thioredoxin and thioredoxin reductase 1 (TR1) are redox proteins that have been implicated in cellular events such as proliferation, transformation, and apoptosis. Analysis of the expression and localization of TR1 in different normal and cancer cell lines and in colon tissues (normal, neoplastic, or inflamed) was performed using reverse transcription-PCR and in situ hybridization. TR1 mRNA was expressed in all analyzed tissues with TR mRNA-positive cells restricted to the stroma of colon crypts, partly being CD3 or CD56 positive. In neoplastic areas of colonic cancer tissue, a loss of TR was obvious. None of the epithelial cells in colonic mucosa expressed TR mRNA, whereas more than 70% of HT-29 cells grown in monolayer were positive for TR. In contrast, HT-29 cells, grown as spheroids or as tumors in SCID mice, were negative for TR. In contrast to these in vitro findings and previous studies, there is no evidence that TR plays a significant role in vivo in normal cell growth in colonic epithelial cells. The mechanism underlying the loss of TR1-positive/CD3-positive/CD56-positive cells or the biologic consequence of this phenomenon observed in neoplastic colonic tissue remains to be clarified.