Abstract The aim of this study was to evaluate the clinical relevance of blood parameters as circulating tumor cells (CTCs) and HLA subtype in renal cell carcinoma (RCC) patients. 233 peripheral blood samples from 154 RCC patients were tested for the presence of disseminated tumor cells (DTCs) by using the autoMACS technique and immunocytochemical (ICC) staining of cytokeratin. The frequency of CTCs was analyzed statistically and correlated with relevant clinical data. In addition, HLA subtype was analysed for 91 out of the 154 RCC patients and for 203 healthy blood donors. A statistical comparison was performed. After following the CD45 autoMACS depletion protocol, we identified CTCs in 96 out of 233 peripheral blood samples (41%), which originated from 81 out of 154 (53%) RCC patients. Besides a significant correlation between the detection of CTCs before and after primary tumor resection a significant association with prognosis was found (p < 0.002; X2-test). RCC patients with CK+ CTCs in their peripheral blood had a 5 times increased risk of tumor-related death compared to patients without these cells. In a Kaplan-Meier-Analysis these results were confirmed (p < 0.001). On one hand, RCC patients had less alleles HLA-Cw*07 (p < 0.05; X2-test) and HLA-DRB1*04 (p < 0.05; X2-test) compared to healthy blood donors. On the other hand, RCC patients showed an increased occurrence of the allele HLA-Cw*12 compared to healthy blood donors. However, this difference was not significant. In summary, for RCC patients the presence of CTCs was associated with a poor overall survival and significantly correlated with an increased risk of tumor-related death. Detection of CK+ CTCs in peripheral blood is a significant and independent prognostic factor for renal cell carcinoma patients. Occurrence of the alleles HLA-Cw*07, and HLA-DRB1*04 was significantly reduced in RCC patients compared to healthy blood donors and may reduce the risk to suffer from a RCC. Citation Format: Steffen Goebel, Karen Bluemke-Anbau, Wolfgang Altermann, Udo Bilkenroth, Axel Meye, Susanne Fuessel, Christine Lautenschlaeger, Andres Melchior, Hans Heynemann, Paolo Fornara, Helge Taubert. Blood parameters in renal cell carcinoma patients can have prognostic impact and differ from those of healthy blood donors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 57. doi:10.1158/1538-7445.AM2014-57