Background The objective of our study was to estimate trends in cancer incidence and mortality in France over the period 1980–2005. Methods Twenty-five cancer sites were analyzed. Incidence data for the period 1975–2003 were collected by 17 departmental registries, covering approximately 16% of the population. Mortality data for the period 1975–2004 were provided by Inserm. The estimate of national incidence was based on the use of mortality as a proxy for incidence, as mortality data were available at the departmental and national levels. Observed incidence and mortality data were modeled using an age-cohort model that included an interaction term. The numbers of new cancer cases and cancer deaths in 2005 were derived from short-term predictions using statistical modeling. Results In 2005, the number of new cases was estimated at 320,000, representing an 89% increase since 1980. Nearly half of this increase was due to demographic changes. The remaining portion was largely explained by the increase in the incidence of prostate cancer in men and breast cancer in women. The age-standardized incidence rate for the global population increased by 39%. The number of deaths was estimated at 146,000 in 2005, representing a 13% increase since 1980. This increase in the number of deaths is much lower than that predicted by demographic changes (37%). The age-standardized mortality rate decreased by 22%. This decline was more pronounced from 2000 to 2005 for both sexes. The incidence and mortality of alcohol-related cancers continued to decline among men. The incidence and mortality of lung cancer among women continued to rise: this cancer was the second leading cause of cancer death among women. The incidence of breast cancer has risen steadily, while mortality has declined since the late 1990s. Conclusion These new estimates covering the period 1980–2005 confirm the significant divergence between cancer incidence and mortality trends in France. This divergence is explained by the combined effect of the decrease in the incidence of the most aggressive cancers and the increase in the incidence of cancers with a better prognosis, this increase being linked, in part, to changes in medical practices, leading to earlier diagnoses. (R.A.)