Purpose: The objective of the study was to analyze the clinico-pathological differences and the oncologic outcomes between right and left-sided colon cancer. Patients and methods: The patients cohort was identified from a prospective register of colon cancer, 950 patients underwent surgery (stages I, II and III), of which 431 had right-sided colon cancer and 519 had left-sided colon cancer. Results: More laparoscopic resections were performed (101 vs 191; p < 0.001) and operating times were longer (146 min vs 165 min; p < 0.001) in the left-sided colon group. Patients with right-sided colon cancer more frequently received transfusions (18.8% vs 11.3%; p < 0.001) and experienced a greater number of complications (28.5% vs 20.9%, p = 0.004), although severity and operative mortality were similar in both groups (1.2% vs 0.2%). Mucinous adenocarcinomas and undifferentiated tumors were more frequent in the right-sided group (12% vs 6.5%; p < 0.001). Early stage was predominant in the left-sided colon tumors (28.2% vs 34.5%, p = 0.02). There were no differences in disease-free survival (DFS) in stages I and II after a median follow-up of 103 months. However, a greater survival at five and ten years in left-sided, stage III tumors was observed, with a trend towards statistical significance (p = 0.06). No differences were found with regard to the patterns of recurrence. Conclusions: Right-sided colon cancer exhibits phenotypical differences with regard to left-sided colon cancer. In stage III disease, left-sided colon cancer has a greater survival with a trend towards statistical significance. Overall, tumor location is a variable that should be taken into consideration in clinical studies of colon cancer.