Background: Generally, the incidence rate of colorectal cancer (CRC) is increasing among young patients (aged <49 years), while the reasons for the rising incidence are unclear. Indicative variables, such as tumour location, gender preference and genetic preponderance have not been followed up in a consistent manner. The current study was primarily conducted to improve the hereditary CRC screening programme by assessing the demographic and pathological characteristics of early-onset CRC compared to late-onset CRC in northeast Iran. Methods: This retrospective study was carried out over a three-year follow-up period (2014-2017) and included 562 CRC patients in three Mashhad City hospital laboratories in north-eastern Iran. We applied comparative analysis of pathological and familial features together with information on the presence of genetic mismatch repair-deficiency in relation to final patient status (surviving versus deceased cases). Analyses using R studio software were performed on early-onset CRC (n=222) and late-onset CRC (n=340) groups produced by division at the age of 50 years. Results: From an age-of-onset point of view, the distribution between the genders differed with females showing a higher proportion of early-onset CRC compared to men (56% vs. 44 %) , while the late-onset CRC disparity was less pronounced (48% vs. 52%). The mean age of all participants was 55.6 ± 14.8 years, while it was 40.3 ± 7.3 years for early-onset CRC and 65.1 ± 9.3 years for late-onset CRC. With respect to anatomical tumour location (distal, rectal, and proximal), the frequencies were 61%, 28% and 11%, respectively, but the variation did not reach statically significance. There was a dramatic difference with regard to the history of CRC in second-degree relatives (SDR) and that of the combination of first-degree relatives and SDR (p=0.001 and p=0.03, respectively). Expression of the MLH1 and PMS2 genes were significantly different between survivors and deceased, however this finding was not observed with regard to the MSH6 and the MSH2 genes. Conclusion: The variation of demographic, pathological and genetic characteristics of CRC between early-onset and late-onset cancers of this kind emphasizes the need for a well-defined algorithm to identify high-risk patients.