Obesity has been associated with increased colon cancer risk in epidemiological studies; however, the specific time periods during which obesity may be most relevant as well as how changes in adult body size over time affect colon cancer risk have not been well explored. We evaluated potential associations between BMI in each age decade(20s, 30s, 40s, 50s, and 2 years before study recruitment (“recruitment period”)) and in BMI changes over timeand colon cancer risk in a population-based case–control study comprising 438 cases and 491 controls. We found that obese (BMI ≥ 30.0 kg/m2) compared to normal (BMI ≥ 18.5 to <25.0 kg/m2) body size at the recruitment period was associated with increased colon cancer risk (odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.03−2.31; P = 0.03). No associations were observed for obese body size in the other age decades. An increased risk was found for changes in BMI between the 30s decade and the recruitment period of 5–10 kg/m2 (OR = 1.54; 95%CI = 1.02−2.34; P = 0.04) and >10 kg/m2 (OR = 2.40; 95% CI = 1.23−4.66;P = 0.01) (P trend = 0.01). Stratification by gender revealed that BMI changes >10 kg/m2 increased risk in women but not men. Similar results were found for BMI changes between the 20s decade and the recruitment period but effect sizes were smaller. Our results provide additional support to obesity's role in colon cancer and suggest large body size increases exceeding 10 kg/m2 may potentially be more important after age 30, particularly among women; however, prospective studies with sex hormone, growth factor, and pro-inflammatory biomarkers are needed to provide insights to the underlying biological mechanism(s).