DNA-directed RNA polymerase II subunit F (POLR2F), a subunit of the V0 domain of the vacuolar ATPase (ATP6V0A1) and the prion protein (PRNP) are molecules of potential importance in carcinogenesis and targeted cancer therapy. However, their expression has not been studied in colorectal carcinomas.Expression microarray data were analyzed using a novel computational tool to reveal elevated levels of POLR2F, ATP6V0A1 and PRNP in relapsed colorectal carcinoma patients. The mRNA levels of POLR2F, ATP6V0A1 and PRNP were evaluated by quantitative RT-PCR in 70 colorectal carcinomas and 17 normal tissue specimens and were correlated with clinicopathological parameters.POLR2F and PRNP were up-regulated in colorectal carcinomas. Moreover, a significant difference in the expression levels of all three molecules between the right colon and the rectum was observed. High expression levels of POLR2F and ATP6V0A1 correlated with improved 3-year survival. Moreover, PRNP expression constituted an independent prognostic factor of the 3-year survival in multivariate analysis.POLR2F and PRNP exhibited elevated levels in carcinomas compared to normal tissue samples suggesting a possible role for these molecules in colorectal cancer. The association of the three molecules with survival or disease prognosis warrants further investigation.