Hemophagocytic syndrome (HPS) is a rare condition caused by dysregulated activation of the immune system leading to infiltration of bone marrow and organs by nonmalignant macrophages that phagocytose blood cells. Primary HPS is caused by inherited immune dysregulation whereas secondary HPS is triggered by neoplastic, infectious or autoimmune diseases. Clinically, the syndrome presents with continuous high-grade fever in association with multi-organ involvement. Few data are available regarding renal manifestations of HPS. We report a 60-year-old patient with NK/T cell nasopharyngeal extranodal lymphoma who presented with acute kidney injury and nephrotic range proteinuria in association with fever and pancytopenia. A kidney biopsy was consistent with collapsing glomerulopathy. A final diagnosis of HPS was made on the basis of clinical, laboratory, and bone marrow biopsy findings in accordance with established diagnostic criteria. Steroid therapy was initiated. However, the patient failed to recover his renal function and remained hemodialysis-dependent. Key diagnostic and therapeutic challenges and strategies used to overcome those challenges are discussed.