In preparation for any type of forthcoming colorectal cancer (CRC) mass screening we examined trends in CRC incidence and mortality according to sex, subsite and age in southern Netherlands. Population-based data from the Eindhoven Cancer Registry during the period 1975-2004 were used. Age-period-cohort analyses were performed to investigate possible aetiologic, diagnostic or therapeutic origins of the trends. Age-adjusted (European Standardized Rates) incidence rates for colon cancer increased since 1975 from 23 in 100 000 for both sexes to about 38 in 100 000 for males and 30 in 100 000 for females in 2004. Incidence of rectal cancer remained relatively stable at about 25 in 100 000 males and 15 in 100 000 females. The incidence of CRC increased for male patients from birth cohorts between 1900 and 1955 (P = 0.010), especially in left-sided colon cancer in the younger birth cohorts [RR1900: 0.8 (95% confidence interval, CI: 0.6, 1.0), RR1960: 1.6 (95% CI: 0.9, 2.8), reference: 1910-1919]. For women a similar, although weaker increase in CRC incidence was found. Mortality rates for CRC started to decrease in 1975, more pronounced for rectal than for colon cancer. The relative risk for dying in men with CRC decreased from 1.3 (95% CI: 1.0, 1.6) in the 1900 birth cohort to 0.1 (95% CI: 0.1, 0.4) in the 1960 birth cohort, reference 1910-1919 birth cohort. The increasing incidence and decreasing mortality in CRC is largely affected by birth cohort effects. Changes in CRC incidence are likely to be attributed to lifestyle factors and decreasing mortality is due to earlier detection and improved treatment, especially among younger patients. European Journal of Cancer Prevention 18:145-152 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.