Increasing evidence suggests genetic, biological and demographical difference between right and left colon cancer. Studies have also indicated age differences in the pathology of colon cancer. There is a scarcity of large-scale studies that closely examine the pathological differences regarding age and tumor location. The aim of our study was to do an extensive comparison of right- and left- sided colon cancers as well as comparing patients <50 years with older patients. A retrospective, population-based study was carried out on all patients with colon cancer in Iceland between 1955 and 2004. A total of 2293 cases were analyzed (1148 men, 1145 women). All histopathology material was re-evaluated. Differences in tumor characteristics between right and left location and younger (<50) and older (≥50) patients was evaluated in particular. Higher TNM-stage, larger tumors, vessel invasion, mucinous type, high grade and expanding tumor border occurred more frequently in right- versus left-sided lesions while annular and polypoid tumors were more common in left-sided tumors (p < 0.05). Young patients had more frequent lymph node metastases, vessel invasion, nonpolypoid lesions and infiltrating tumor border (p < 0.05). Right-sided lesions show more aggressive features, reflected in morphology and stage. Younger patients present more frequently with adverse features than do older patients. Frequency of right- and left-sided colon cancer differs by age with pronounced age-location differences in females. This supports the assumption of differences in etiology and carcinogenesis of right- and left-sided colon cancer, and between young and old patients.