Abstract Background: Colorectal Cancer is the 5th common malig-nant tumor among Egyptians representing 5% of the total cancers according to National Cancer Registry 2013. Aim of Study: To evaluate association of serum level of Cyclin D1 and variants in MicroRNA196a-2 (miR196A2) rs11614913 and Deleted in colorectal cancer (DCC) rs714 genes with the risk of colorectal cancer and its progression. Patients and Methods: A case-control study was done on 100 colorectal cancer (CRC) patients and 60 healthy controls were enrolled and were genotyped for miR196A2 rs11614913 gene variation using the real time-Taq Man assay and DCC rs714 gene variation using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Serum levels of Cyclin D1 were measured by Enzyme linked immunosorbant assay (ELSA). Results: Pathogenic variant G of DCC was associated with an increased risk of colorectal cancer compared to A variant (p<0.001). Also, G variant (GG and GA genotypes) was associated with increased risk of distant metastasis in patients of CRC compared to DCC A variant (p=0.014). There was a significant association between increased serum level of Cyclin D 1 and the risk of colorectal cancer (p=0.001) with cut-off value >3.4ng/mL. Pathogenic variant C of miR196A2 was not significantly associated with increased risk of colorectal cancer (p=0.766) but showed a significant increase in tumor progression (p=0.013). Conclusion: Pathogenic variant G of DCC and increased serum level of Cyclin D1 are predictive factors of sporadic colorectal cancer among Egyptian patients. C variant of miR196A2 can be used as prognostic rather than diagnostic markers of CRC.