BACKGROUND: Studies of colorectal cancer (CRC) have suggested different mechanisms of carcinogenesis in men and women, young and old patients, right- and left sided tumors, and sporadic and familial tumors. These differences might be reflected in morphology. METHODS: CRCs from 1613 patients operated on in 2004-2006 in Sweden were histologically reviewed. Morphology was examined in relation to sex, age groups, location, and family history. RESULTS: Tumors in the right colon were larger, of higher stage, more often poorly differentiated, more mucin-producing, more often had a peritumoral lymphocytic infiltrate and a high level of tumor-infiltrating lymphocytes (TILs), and more seldom had an infiltrating margin than tumors in the left colon and rectum (p < 0.0001 for most features). Young patients (<60 years) more seldom had multiple tumors but more often had perineural invasion, an infiltrative tumor margin, and high-stage tumors. Three features, TILs, medullary tumors, and invasive tumor margin, were related to sex. Only vascular invasion was related to familiality. CONCLUSION: Location is the factor that has the most influence on tumor morphology. The results support the idea that different carcinogenic mechanisms may be involved in the right and left colon. Age is the most important determinant for the presence of multiple tumors and is a crucial factor for the aggressiveness of the disease.