Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome which can be an inherited congenital disorder or can develop secondary to malignancy, infection, or autoimmune disease. Secondary HLH due to malignancy occurs most commonly with T or NK-cell lymphoid neoplasms. HLH with B-cell malignancies is less common and HLH has rarely been described in association with precursor B-cell acute lymphoblastic leukemia (B-ALL). We report three cases of HLH associated with B-ALL and review 17 cases of ALL-associated HLH previously reported in the literature.