A large body size may differentially influence risk of colorectal cancer (CRC) by anatomic location. The Netherlands Cohort Study includes 120,852 men and women aged 55-69 years who self-reported weight, height, and trouser/skirt size at baseline (1986), as well as weight at age 20 years. Derived variables included body mass index (BMI; weight (kg)/height (m)(2)), BMI at age 20 years, and BMI change. After 16.3 years of follow-up (1986-2002), 2,316 CRC cases were available for case-cohort analysis. In men, the highest risk estimates were observed for body fat (per 5-unit increase in BMI, hazard ratio (HR) = 1.25, 95% confidence interval (CI): 1.05, 1.46; for highest quintile of trouser size vs. lowest, HR = 1.63, 95% CI: 1.17, 2.29 (P-trend = 0.02)) and appeared more closely associated with distal colon tumors (for BMI (5-unit increase), HR = 1.42, 95% CI: 1.13, 1.79; for highest quintile of trouser size, HR = 2.56, 95% CI: 1.55, 4.24 (P-trend <0.01)) than with proximal colon or rectal tumors. In women, body fat was not associated with CRC risk unless it was considered simultaneously with physical activity; a large trouser/skirt size and a low level of physical activity increased risk for all subtypes. Height was associated with risk of CRC, especially distal colon tumors (highest quintile vs. lowest: HR = 1.53, 95% CI: 1.03, 2.27; P-trend = 0.05), in women only.