The increase in nuclear localization of SMAD3 in our in vivo and in vitro models of chemoresistance together with the modulation of TGF-β target genes only in chemoresistant, 5FU-treated, colon carcinoma cells led us to hypothesize a possible role of the TGF-β molecule in the response to 5FU. This evidence concerns the gene SMAD3 and colon carcinoma.