Several studies report varying incidence rates of cancer in subsites of the colorectum, as an increasing proportion appears to develop in the proximal colon. Varying incidence trends together with biological differences between the colorectal segments raise questions of whether lifestyle factors impact on the risk of cancer differently at colorectal subsites. We provide an updated overview of the risk of cancer at different colorectal subsites (proximal colon, distal colon, and rectum) according to BMI and physical activity to shed light on this issue. Cohort studies of colorectal cancer, published in English throughout 2010, were identified using PubMed. The risk estimates from 30 eligible studies were summarized for BMI and physical activity. A positive relationship was found between BMI and cancer for all colorectal subsites, but most pronounced for the distal colon [relative risk (RR) 1.59, 95% confidence interval (CI) 1.34-1.89]. For the proximal colon and rectum, the risk estimates were 1.24 (95% CI 1.08-1.42) and 1.23 (95% CI 1.02-1.48), respectively. Physical activity was related inversely to the risk of cancer at the proximal (RR 0.76, 95% CI 0.70-0.83) and distal colon (RR 0.77, 95% CI 0.71-0.83). Such a relationship could not be established for the rectum (RR 0.98, 95% CI 0.88-1.08). In conclusion, the results suggest minor differences in the associations of BMI and the risk of cancer between the colorectal subsites. For physical activity, the association does not seem to differ between the colonic subsites, but a difference was observed between the colon and the rectum, perhaps indicating that different mechanisms are operating in the development of colon and rectal cancer.