The socioeconomic and health context differs significantly between the overseas departments and regions (DROM) and mainland France. Breast cancer is the most common cancer among women and the leading cause of cancer death in women worldwide, including in the DROMs. Its incidence rate is lower in the DROMs than in mainland France. It is necessary to analyze the performance of organized breast cancer screening in the DROMs separately and to compare the results with those of mainland France. This study presents the trends in performance indicators for the organized breast cancer screening program between 2008 and 2018 in the four DROMs—Guadeloupe, Martinique, French Guiana, and Réunion—and compares them to those of mainland France. While screening participation rates in Guadeloupe, Martinique, and Réunion are similar to those in mainland France, the rate in French Guiana is significantly lower. These rates increased over the study period in Guadeloupe and decreased in the other three DROMs. Screening results vary from one DROM to another and depending on the stage of the screening process (first or second reading, before or after follow-up). In French Guiana, the rates of positive screenings (abnormality detection rates) are generally lower. In 2017–2018, the rates of detected cancers in the four DROMs were lower than in almost all mainland departments, particularly in French Guiana, where they were significantly lower. The positive predictive values in the first screening round, both before and after further evaluation, were all lower than those in mainland France. The lower rates of detected cancers in the DROMs could be explained by a lower incidence of breast cancer in these territories and by poorer screening performance. More comprehensive data collection on the type and size of the detected cancer would allow for a more detailed analysis of the program’s performance in terms of cancer detection.