Despite their 84% protein sequence homology and similar mode of activation, increasing evidence indicates that SMAD2 and SMAD3 perform distinct and opposing functions during tumor progression, including cell invasion, tumor growth, and metastasis [18,22,23], suggesting that SMAD2/SMAD3 expression or activation ratio could be determining factors in the pro- or anti-tumorigenic roles of TGFβ. This evidence concerns the gene SMAD3 and neoplasm.