Background: Familial polyposis coli (FPC) is almost always benign lesions presenting by bleeding or discovered accidentally during routine colonoscopy. However, malignant transformation could not be excluded and this necessitates early detection in the metaplasia stage. Aim: Evaluation of the ability of estimated tissue expression levels of microRNA-663b (MiR-663b) to distinguish benign from malignant rectal polyps in patients with FPC. Subjects & Methods: Forty-one patients with FPC were assessed clinically, had colonoscopic biopsies, and provided blood samples for estimation of serum carcinoembryonic antigen (CEA) and cancer antigen 19-9 estimate (CA19-9). Tissue samples were separated into two portions, for pathological analysis and PCR analysis to determine the degree of MiR-663b expression in the tissue. Subjects undergoing colonoscopy for other reasons were subjected to a rectal biopsy.Results: The serum levels of CA 19-9 were considerably greater in MRP patients compared to healthy controls. The estimated tissue level of MiR-663b in three benign specimens was greater than the 4th quartile level of control specimens and in the range between the 1st and 2nd quartile levels of malignant specimens; these specimens were thus classified pre-malignant. A multivariate Regression analysis identified elevated miRNA366b gene expression as an independent risk factor for BRP malignant transformation.Conclusion:MiR-663b tissue expression estimation might be utilized to distinguish benign from malignant colorectal polyps. Whenever MiR-663b levels were greater than control levels but below than the levels diagnostic of malignancy, are able to predict the early malignant transformation of benign polyps prior to their being identified by pathology.