Colorectal cancer (CRC) is one of the most common malignant neoplasms in Egypt, and interestingly in young age. Adenomatous polyps and inflammatory bowel diseases (IBD) are considered the commonest pre-malignant lesions for CRC. A possible diagnostic role for different microRNAs on CRC has been suggested by numerous studies. To assess the serum expression of 3 microRNA markers (miR-29a, miR-92a and miR-145) in pre-malignant and malignant colorectal lesions. The 60 patients studied were divided into 4 groups: CRC group (25 patients), IBD group (11 patients), adenomatous polyps group (14 patients) and control group (10 patients). The serum expression of the 3 markers (miR-29a, miR-92a and miR-145) has been assessed by RT-PCR. All CRCs were sporadic cases. Significant downregulation of miR-145 in CRC group was reported at all levels, i.e. when compared to normal, among the 3 studied groups, and when compared between CRC and non-CRC groups. Significant upregulation of miR-29a in CRC was reported when compared to normal, but no significant difference existed either among the 3 studied groups or between CRC and the other 2 groups. All 3 miRNAs studied were positively inter-correlated. miR-145 may be considered a promising non-invasive reliable diagnostic marker in CRC. Extended studies are needed to ascertain the diagnostic role of miRNAs in CRC.