Background: Colorectal cancer (CRC) has high morbidity and mortality rates. Invasive techniques and other laboratory tests with variable sensitivity and specificity are currently used in diagnosis. Micro ribonucleic acids (miRNAs) have bio vital roles in cell proliferation and apoptosis. Dys-regulation of miRNAs is linked to tumour genesis. The objective of this study was to evaluate the specificity and sensitivity of serum non-invasive biomarkers (micro-RNAs), miR-1246, miR-23a, and miR-451in CRC patients. Methods: Peripheral expression of three miRNAs (miR-1246, miR-23a and miR-451) was investigated in sera of 37 CRC Egyptian patients and 30 healthy controls, using quantitative real-time polymerase chain reaction trying to reach the optimal non-invasive combination of miRNAs. Results: Serum miR-1246 was up-regulated in sera of CRC patients compared to normal controls (fold change = 3.55; P< 0.001) and showed 100% sensitivity and 80% specificity in diagnosis of CRC. Serum miR-451 was significantly down-reg- ulated in CRC patients (fold change = -4.86; p= 0.014), whereas, miR-23a was down-regulated but this was not statistically significant. Conclusion: Up-regulation of miR-1246 and down-regulation of miR-451 in the sera of primary CRC Egyptian patients were confirmed with high sensitivity and specificity. Large-scale studies on a wider spectrum of miRNAs in Egyptian CRC patients are needed. Keywords: miR-1246; miR-451; miR-23a.