We herein evaluate the role of the B7-family molecule CD86 and the Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) as a possible immunopathogenic factors in patients with ALL. The results of 60 patients with de novo ALL were compared to 40 controls. A significant statistical difference between CD86 expression and sCTLA-4 levels in patients versus their controls has been detected. During follow up period of 28 months, patients suffered from relapse (16 patients) had significantly higher CD86 expression and sCTL-4 levels compared to those remained in complete remission (44 patients) (p = 0.005 and 0.03 respectively). Patients who died from the disease (9 patients) showed significantly higher CD 86 expression and sCTLA-4 levels than surviving patients (51 patients) (p = 0.004 and 0.01 respectively). In conclusion, the higher levels of sCTLA-4 and CD86 in B-ALL patients might be candidate parameters for poor prognosis and may serve to refine treatment stratification with intensification of therapy in those patients prone to relapse.