Standard chemotherapic approach for MZL is missing. We are presenting our monocenter experience with 2CdA+/-rituximab. Patients received 2CdA, 5mg/m(2), weekly, for 6 weeks. Patients receiving rituximab underwent to antibody administration in association with 2CdA, or after the end of chemotherapy. Global ORR was 89.3%, with 53.6% CR, with 60 months of median of TTF. 2CdA and rituximab led to 96.5% ORR, with 60.3% CR, while 2CdA alone to 73.1% ORR, with 38.5% CR. TTF median was reached at 35 months with 2CdA alone; not reached yet in the combination arm. Considering subgroups of MZL, combination therapy has a more favorable outcome in SMZL and NMZL, while MALT does not differ. However, all subgroups present a delayed relapse. Considering minimal residual disease (MRD), adding of rituximab converted 65.0% to negativity versus 15.4% of 2CdA alone, with TTF in positive patients reached after 34 months; not reached yet in negatives. Concomitant use of rituximab with 2CdA allowed an ORR of 98.0%, with 68% CR and 56.3% of MRD conversion, while consequent use 100%, 54.6%, and 70.8%, respectively. TTF does not differ. 2CdA therapy is effective in the treatment of MZL. Adding rituximab allows increasing ORR and CR, prolonging TTF.