We sought to evaluate the expression of HSP27 and HSP90 chaperones in renal cell carcinomas as a target for cancer therapeutics.A total of 127 clear cell renal cell carcinomas stratified according to the Mayo Clinic SSIGN (size, staging, grading, and necrosis) risk groups (good, 1; poor, 5) and 20 cases with metastases, were available. Immunostaining for both HSP27 and HSP90 was performed on tissue microarrays. Results were detailed per scorable arrays per SSIGN risk groups.Immunolabelling for HSP90 and HSP27 was seen in 109 of 127 (86%) and 114 of 127 (89%) cases, respectively. HSP90 scored 4.9 in 32 cases risked SSIGN 1, 3.5 in 41 cases SSIGN 2, 4.8 in 11 cases SSIGN 3, 4.2 in 22 cases SSIGN 4, and 5.0 in three cases SSIGN 5. HSP27 scored 4.6 in 33 risked SSIGN 1, 3.1 in 43 SSIGN 2, 2.6 in 11 SSIGN 3, 3.6 in 24 SSIGN 4, and 2.7 in three SSIGN 5. Metastases ranged from 2.9-5.0. A trend of increasing value for HSP90 was observed when comparing SSIGN 1-2 versus SSIGN 3-5 risk groups (4.2 versus 4.6 mean values; p = 0.06); no difference has been observed for HSP27 (3.8 to 3.9; p = 0.08).A score modulation of HSPs is observed in renal cell carcinoma and may affect the efficacy of targeted therapy.