Previous studies have demonstrated deregulation of the expression and changes in the intracellular distribution of TGF- β pathway components in human endometrial cancer (EC). The aim of this study was to assess the relationship between the expression of TGF- β cascade components, including TGF- β receptor type I (TGFβ RI) and type II (TGFβ RII), SMAD2, SMAD3, SMAD4, and clinicopathological features- tumor grade, FIGO classification, and depth of myometrial invasion- of type I (endome trioid- type) ECs to give some insight into the role of TGF- β cascade components in endometrial tumorigenesis. The expression of TGFβ RI, TGFβ RII, SMAD2, SMAD3, and SMAD4 was evaluated both at the mRNA and protein level using reverse transcription polymerase chain reaction (RT- PCR) and ELISA, respectively. Infiltrating endometrial carcinomas (less and more than half of the myometrial wall thickness) express significantly higher TGFβ RII protein level compared with non- infiltrating tumors (P = 0.04 and P = 0.01, respectively). Decreased level of SMAD2 and SMAD4 mRNAs was observed in the uterine tumors infiltrating less and more than half of the myometrial wall (P = 0.03 and P = 0.02, respectively) compared with noninfiltrating ECs. Significantly higher SMAD4 protein level in the cytoplasmic fraction of ECs was found when tumor grade and depth of myometrial invasion were considered (P < 0.05). Generally, tumor progression was associated with a decreased number of cases characterized by the presence of SMADs in the nuclear fraction only. Our data suggest that disturbances of the TGFβ RII and SMAD4 expression as well as localization of SMADs may be important to the infiltration of the myometrial wall by the type I endometrial carcinomas. Previous studies have demonstrated deregulation of the expression and changes in the intracellular distribution of TGF- [beta] pathway components in human endometrial cancer (EC). The aim of this study was to assess the relationship between the expression of TGF- [beta] cascade components, including TGF - β receptor type I (TGFβ RI) and type II (TGFβ RII), SMAD2, SMAD3, SMAD4, and clinicopathological features- tumor grade, FIGO classification, and depth of myometrial invasion-of type I (endome trioid-type) ECs to give some insight into the role of TGF-β cascade components in endometrial tumorigenesis. The expression of TGFβ RI, TGFβ RII, SMAD2, SMAD3, and SMAD4 was evaluated both at the mRNA and protein level using reverse transcription polymerase chain reaction ) and ELISA, respectively. Infiltrating endometrial carcinomas (less and more than half of the myometrial wall thickness) express significantly higher TGFβ RII protein level compared with non- infiltrating tumo Decreased levels of SMAD2 and SMAD4 mRNAs were observed in the uterine tumors infiltrating less and more than half of the mytrial wall (P = 0.03 and P = 0.02, respectively) compared with noninfiltrating Significantly higher SMAD4 protein level in the cytoplasmic fraction of ECs was found when the tumor grade and depth of myometrial invasion were considered (P <0.05). Generally, tumor progression was associated with a decreased number of cases characterized by the presence of SMADs in the nuclear fraction only. Our data suggest that disturbances of the TGFβ RII and SMAD4 expression as well as localization as SMADs may be important to the infiltration of the myometrial wall by the type I endometrial carcinomas.