French Guiana is a French Overseas territory with singular features: it has a high prevalence of HIV and HTLV-1, its population is ethnically mixed, with widespread poverty, and up to 20% of the population lives in geographic isolation. In this context, we used registry data to estimate incidence and mortality due to hematological malignancies and to compare them with France and tropical Latin America. ICD codes C90 and C88 were compiled between 2005 and 2014. The direct standardization of age structure was performed using the world population. Survival analysis was performed, and Kaplan–Meier curves were drawn. The overall standardized incidence rate was 32.9 per 100,000 male years and 24.5 per 100,000 female years. Between 2005 and 2009, the standardized incidence rate was 29.6 per 100,000 among men and 23.6 per 100,000 among women, and between 2010 and 2014, it was 35.6 per 100,000 among men and 25.2 per 100,000 among women. Multiple myeloma/plasmocytoma and mature t/NK cell lymphomas, notably adult t-cell lymphoma/leukemia due to HTLV-1 infection, were the two most common hematologic malignancies and causes of death. Non-Hodgkin’s lymphoma incidence estimates were greater than global estimates. After adjusting for age, sex, and type of malignancy, people born in a foreign country independently had a poorer case-fatality rate, presumably reflecting difficulties in accessing care. The epidemiology of hematological malignancies in French Guiana has features that distinguish it from mainland France or from Latin America. The incidence of multiple myeloma and adult t-cell lymphoma/leukemia was significantly greater in French Guiana than in France or other Latin American countries.