It is essential to analyze trends in cancer incidence and mortality in the evaluation of cancer control activities. Previous studies from Japan, however, described trends in cancer incidence and mortality only qualitatively. There have been few studies that evaluated the trends quantitatively. We calculated age-standardized mortality rates (1968-2006) and incidence rates (1968-2002) for overall cancer sites and for each major site (stomach, colorectal, liver, lung, prostate, breast, and uterus) in Osaka. We applied a joinpoint regression model to the trends in incidence and mortality, in order to identify the joinpoint and estimate annual percentage change. Then, we quantified the contribution of individual cancer sites to the change in overall cancer mortality rate. For the sites that made a major contribution, we estimated the contribution of the incidence reduction to the mortality reduction. In Osaka, the overall cancer mortality started to decrease from 1998. The decrease was largely attributable to the reduction of stomach and liver cancer mortality (73% for men, 53% for women). The reduction of mortality from the two cancer sites could be explained by the decrease in their incidences (more than 80% for stomach, approximately 100% for liver). Female breast cancer incidence and mortality were both increased probably due to lifestyle changes and delayed introduction of an effective screening program among Japanese. In conclusion, the decreased overall cancer mortality in Osaka during the study period was mainly due to natural decreases in the incidence of stomach and liver cancer, which were attributable to the decrease in risk factors.