Introduction: This article presents the characteristics of the leading causes of death in mainland France during 2004 and describes trends over the recent period (2000–2004) and the longer term (1980–2004). Methods: The data are drawn from the national database of medical causes of death, compiled annually by CépiDc-Inserm. The various causes are coded and categorized according to the International Classification of Diseases. A selection drawn from the European list established by Eurostat—taking into account major disease groups and specific diseases due to their public health significance—was used for the analysis. The study focuses on the underlying cause of death. The indicators considered are the number of deaths, crude and age-standardized death rates, excess mortality ratios, and coefficients of variation. Results: In 2004, 509,408 deaths from all causes occurred in metropolitan France. The corresponding age-standardized mortality rate is 750.1 per 100,000 inhabitants. For the first time, cancer is the leading cause of death, ahead of cardiovascular diseases and accidents. This hierarchy of causes varies by sex and age. Among women, cardiovascular diseases rank first. Regardless of gender, among those aged 15–24, violent deaths (transport accidents and suicide) are the most common causes of death. Among men, the leading cause of death is suicide among those aged 25–44 and lung cancer among those aged 45–64. Among women, tumors are the leading cause of death from ages 25 to 44, and breast cancer is the leading cause of death from ages 45 to 64. From age 65 onward, cardiovascular disease is the leading cause of death for both men and women. Most mortality rates have declined over time. Between 2000 and 2004, transportation accidents declined sharply, but suicide rates remained stable, and, for women, lung cancer increased significantly. Conclusion: These data indicate a downward trend in death rates that has strengthened since 2000, as well as a shift in the structure of causes, particularly an increase in the proportion of cancer-related deaths. Within this general context, certain causes show contrasting trends, notably suicides, which are not declining, and lung cancer and Alzheimer’s disease, which are on the rise. (R.A.)