The Ohio and Mississippi River Valleys are endemic to histoplasmosis. It is usually self‐limiting in immunocompetent people, but it can cause morbidity and mortality if not detected early in people with an underlying autoimmune disease. Disseminated Histoplasmosis induced hemophagocytic lymphohistiocytosis (HLH) mimicking the flare of an underlying autoimmune disease, is uncommon in the published literature. Disseminated histoplasmosis (DH) can cause multiorgan involvement, especially in a patient with an underlying autoimmune disease. We present the case of a 24‐year‐old female with HLH who was initially treated as a flare of autoimmune disease but later etiology was confirmed as disseminated histoplasmosis on bone marrow histopathological examination.