The expression of the CD20 on adult B-cell acute lymphoblastic leukemia (ALL-B) has generally been associated with a poor prognosis, and several studies have explored the incorporation of rituximab into the therapeutic regimen for adult ALL-B patients, with a positive effect on event-free survival (EFS). We analyzed the prognostic value of CD20 expression and the effect of rituximab for the treatment of Hispanic adult ALL-B patients. We performed a retrospective study of 152 ALL-B patients treated from 2009 to 2016. The patient characteristics and treatment outcomes were analyzed according to CD20 expression (CD20+ vs. CD20-), age group, and treatment with rituximab. CD20 expression was positive for 47.7% of patients (n = 72). Excluding the patients who had received rituximab, the overall survival (OS) was greater for the CD20- patient subgroup than for the CD20+ subgroup (11.2 vs. 6.9 months; 95% confidence interval [CI], 7.43-14.9; P = .008). In the CD20+ subgroup, 10 patients (7.2%) received treatment with rituximab, with 100% reaching complete remission (CR) 4 weeks after treatment. In the 18- to 39-year age group, CD20+ patients treated with rituximab had EFS and OS that was not reached. In addition, for CD20+ patients who received with chemotherapy, EFS was 3.9 months (95% CI, 0.6-7.2 months; P = .025) and OS was 7.2 months (95% CI, 3.37-11.0; P = .013). Multivariate analysis showed that the use of rituximab was independently associated with OS and CR at 4 weeks after induction. CD20 expression in adult ALL-B is associated with decreased OS. Treatment with rituximab can increase OS, EFS, and CR in the 18- to 39-year age group.