Findings of a phase II study in patients with relapsed or refractory extranodal marginal zone lymphoma (rrEMZL) reveal that treatment with high doses of the macrolide antibiotic clarithromycin is safe and effective. In a study cohort of 23 patients with rrEMZL and at least one detectable lesion, six had a complete remission and a further six had a partial response following four 2-week courses (given every 21 days) of oral clarithromycin treatment. At a median follow-up of 2 years, only two patients who were responsive to clarithromycin treatment relapsed, and all patients were alive. Nausea, reported by two patients, was the only major adverse event associated with this treatment; these data support further testing of this agent in phase III clinical trials.