Background: Clinical-Pathological and genomic differences between Right-colon cancer (RCC) and Left-colon cancer (LCC) have been reported, but there is not available information from Latin American countries. Methods: A retrospective cohort study was carried out in patients with RCC and LCC treated from January 1989 to December 2016, in a cancer referral center at Mexico City. Patients were assigned into groups according to the location of the neoplasm defined by colonoscopy. Comparison between groups was performed regarding demographic, clinical, histopathology or survival data, using the Student’s T or Squared chi tests, as appropriate. Multivariate analysis was performed employing the logistic regression model. Survival analysis was addressed using the Kaplan-Meier method, and results were compared using the Log rank test. Results: 1,619 patients were included in this analysis; 806 were women (49.8%) and 813 men (50.2%); mean age was 58.1 years old. RCC was registered in 871 cases (53.8%) and LCC in 748 (46.2%). RCC was significantly associated with low socioeconomic status, low body mass index (BMI), low hemoglobin, low serum albumin, and lower lymphocyte count than LCC. Distribution of TNM stages was similar between groups, as well as gender, age of presentation, comorbidities, surgical morbidity and mortality; 72.3% of RCC and 83.2% of LCC were well or moderately differentiated (p< 0.0001). Mean lymph node retrieval was 19.3 (SD 14.6) for RCC and 15.7 (SD 13.1) for LCC (p< 0.0001). Mean metastatic lymph node ratio was 0.19 for RCC and 0.21 for LCC (p= 0.54). Median Overall survival (OS) was 5.55 years (95% CI 4.3–6.8) for RCC, and 3.28 years (95% CI 2.1–4.45) for LCC (p= 0.052). Conclusions: Striking differences between RCC and LCC were found, mainly represented by anemia and immunonutritional variables. Moreover, OS is substantially better for RCC.