In this study, we found that FAT1 silencing led to an increase in phosphorylated Smad2/Smad3 and nuclear Smad2/Smad3 levels, while overexpression of FAT1 led to a decrease in phosphorylated Smad2/Smad3 and nuclear Smad2/Smad3 levels; these findings indicate that FAT1 inhibits the activity of the TGFβ pathway in DLBCL. This evidence concerns the gene SMAD3 and diffuse large B-cell lymphoma.