Objective To investigate the characters of morphology change and protein expres-sion in progressed renal cell carcinoma after the treatment of sorafinib. Methods Clinical data of 2 cases with progressed renal cell carcinoma treated with sorafenib were collected. The HE slices were reviewed. Immunochemistry was used to detect the expression of Vimentin, AE1/AE3, CK7, CK8, CK18, CD10, VEGF, VEGFR2, p53 and Ki-67 levels. Results There was no difference in patho-logic type between before and after the therapy of sorafenib. Both of the 2 cases were showed degener-ation in tumor cell in different degree with fibrosis and necrosis. The expression of renal cell carcinoma related antigens (Vimentin, AE1/AE3, CK7, CK8, CK18 and CD10) had no difference before and af-ter the treatment of sorafinib. The expressions of VEGF, VEGFR2, p53 and Ki-67 were increased, and the expression of Bcl-2 was decreased after the therapy of sorafinib. Conclusions There may be some morphologie differences between the metastatic tumor or the recurrent tumor and primary tumor because of the treatment of sorafenib. However the pathologic type is the same before and after the treatment of sorafenib. The main differences are the degeneration of the tumor cell and fibrosis after the treatment of sorafenib. The expression changes of VEGF and VEGFR2 may be related to the sor-afenib application.