457 Background: The human S100 proteins are a calcium-binding protein comprising around 20 sort, at least 16 of these genes included pseudogenes are clustering to chromosome 1q21 , known as the epidermal differentiation complex. We have reported that S100A1 and A10 are expressed in human renal cell carcinoma (RCC) (Teratani T et al; Cancer Lett 2002, Teratani T, et al; BBRC 2002, Domoto, et al Cancer Sci. 2007). Diminished expression of S100A2 has been reported in some kinds of cancers (ex. lung, breast, prostate), but not reported in renal cell carcinoma (RCC). The aim of the present study is to evaluate the expression level S100A2 mRNA in human renal cell carcinoma. Methods: Sixty-one patients, pathologically diagnosed for clear cell RCC performed nephrectomy, were used in this study. Genomic DNA and RNA were extracted from RCC part and matched normal part in each patient. First-strand cDNA was synthesized from 2 micrograms RNA using Superscript-2 reverse transcriptase (Invitorgen), and reverse transcription polymerase chain reaction (RT-PCR) were performed using specific primers for S100A2. We also check the CpG methylation in the promoter region of the S100A2 gene using COBRA assay (combined bisulfite restriction analysis). Results: 45 cases (73%) showed decreased S100A2 expression in RCC parts. In53 cases of clear cell RCC, S100A2 expression decreased in fourty-two (79%) cases. In contrast clear cell RCC, 5 cases showed expression S100A2 in non-clear RCC (8cases; 62%), and 2 cases of clear cell RCC in VHL disease patients also had expression of S100A2. 30 cases of clear cell RCC were used in COBRA assay, S100A2 methylation were seen in all cases. Conclusions: Diminished expression of S100A2 is frequently shows in RCC, especially clear cell RCC. It suggests that property of clear cell RCC is different from other type of RCC.