Here we found that by NGS analysis, 21 classical reference genes (including GAPDH, ACTB, RPLP0, PPIA and B2M) pertaining to biological functions and processes including cell cycle, ribosome biogenesis, glycolysis, angiogenesis, apoptosis and inflammation and commonly used for the normalization of gene expression in qPCR studies, had differential expression in CRC tumors vs. normal tissues. The gene discussed is PPIA; the disease is colorectal carcinoma.