A 59-year-old male with a history of follicular lymphoma presented with fever, pancytopenia, and disseminated lesions, ultimately leading to multi-organ failure. The patient, originally from El Salvador, had recently received chemotherapy. Post-mortem examination and PCR analysis confirmed fulminant reactivation of Trypanosoma cruzi, specifically the TcI genotype, causing widespread amastigote infection in various organs, including the heart and brain. Despite treatment with benznidazole, the infection was fatal. This case highlights the critical importance of considering T. cruzi reactivation in immunocompromised patients from endemic areas, even in the absence of typical Chagas disease symptoms. Teaching point: Chagas disease reactivation in immunocompromised patients can be fulminant and fatal, requiring high clinical suspicion.