A 46 years old African-American male with a refractory large-B cell lymphoma presented with fever and neutropenia. An extensive infectious disease workup failed to determine an etiology for the fever, which persisted despite antimicrobial therapy escalation. Workup for a suspected hemophagocytic lymphohistiocytosis (HLH) was initiated, in which the patient met six out of nine criteria (five required): Fever, neutropenia, elevated soluble CD25, triglyceride, and ferritin, hemophagocytosis in the bone marrow (Figure), normal spleen, normal NK function, and undetermined CXCL9 level (last three representing unmet criteria) [1]. Hence the diagnosis of a lymphoma-triggered HLH. Treatment with dexamethasone and a salvage chemo-regimen of rituximab, ifosfamide, carboplatin, and etoposide (R-ICE), resulted in a lymph node response, fever resolution, and HLH criteria improvement. HLH is an aggressive and potentially fatal syndrome of excessive immune activation [2]. Familial or sporadic cases are triggered mostly by infection and malignancy [2]. Prompt diagnosis and treatment is critical to prevent death.