KEYWORDS ALCL HLH treatment Diagnostic TOPICS Medicine Oncology ABSTRACT large cell lymphoma (ALCL) is a rare paediatric non-Hodgkin lymphoma. Its course can be complicated by haemophagocytic lymphohistiocytosis (HLH), a severe hyperinflammatory syndrome. The case is presented of a 2-year-old boy with ALCL and secondary HLH, to highlight the treatment course and complications. The boy initially presented with upper respiratory symptoms and cervical lymphadenopathy; biopsy confirmed ALCL. Initial complications during the ALCL 99 Program were managed, allowing treatment to continue. A few months later, he was readmitted with fever, pancytopenia, elevated ferritin, hypertriglyceridaemia, and hepatosplenomegaly. These symptoms led to an HLH diagnosis overlapping the previously diagnosed ALCL. Despite treatment in the ICU, multi-organ failure occurred leading to death. Secondary HLH significantly worsens the ALCL clinical course. Poor outcomes despite standard HLH-directed therapies emphasize the critical need for earlier recognition and more effective strategies.