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There is a growing amount of data suggesting that carcinomas of the right and left colon should be considered as different tumor entities. Using the data and analysis compiled in the German multicentered study “Colon/Rectum Cancer,” we aimed to clarify whether the existing differences influence clinical and histological parameters, the perioperative course, and the survival of patients with right- vs left-sided colon cancer.During a 3-year period data on all patients with colon cancer were evaluated. Right- and left-sided cancers were compared regarding the following parameters: demographic factors, comorbidities, and histology. For patients who underwent elective surgery with curative intent, the perioperative course and survival were also analyzed.A total of 17,641 patients with colon carcinomas were included; 12,719 underwent curative surgery. Patients with right-sided colon cancer were significantly older, and predominantly women with a higher rate of comorbidities. Mortality was significantly higher for this group. Final pathology revealed a higher percentage of poorly differentiated and locally advanced tumors. Rate of synchronous distant metastases was comparable. However, hepatic and pulmonary metastases were more frequently found in left-sided, peritoneal carcinomatosis in right-sided carcinomas. Survival was significantly worse in patients with right-sided carcinomas on an adjusted multivariate model (odds ratio, 1.12).We found that right- and left-sided colon cancers are significantly different regarding epidemiological, clinical, and histological parameters. Patients with right-sided colon cancers have a worse prognosis. These discrepancies may be caused by genetic differences that account for distinct carcinogenesis and biological behavior. The impact of these findings on screening and therapy remains to be defined.