Background: The Roussillon chemical complex, located in the Rhône Valley, 50 kilometers south of Lyon, is one of France’s major chemical sites. This study aims to address concerns raised by local residents regarding an excess of environmentally-related cancers among the population living near the site. Method: The study compares cancer incidence rates and cancer mortality rates in the six municipalities adjacent to the complex with those observed in the Isère department over the 2003–2013 period. The results regarding pleural mesothelioma led to the expansion of the descriptive analysis with an etiological study. This study is based on an analysis of surveys conducted as part of the National Mesothelioma Surveillance Program (PNSM), which trace past asbestos exposures among individuals diagnosed with this cancer. Results: The incidence of pleural mesothelioma and the mortality rate for this disease are, among men, more than five times higher in the Roussillon sector than in the Isère department. To a lesser extent, a slight excess mortality from lung and laryngeal cancers is observed for both sexes. No other excess cancer sites were found in the area. Analysis of PNSM data confirms the occupational origin of the mesotheliomas, as nearly all cases reported occupational exposure to asbestos at a company within the Roussillon industrial complex. Conclusion: This study shows that living near the Roussillon chemical complex is not associated with an overall excess of cancer. The complementary nature of data from the cancer registry and the PNSM confirms the occupational origin of pleural mesotheliomas, which are observed in high excess in the area.