Ocular adnexal lymphomas (OALs) are typically low-grade lymphomas and are largely represented by marginal-zone lymphomas (EMZL). Radiotherapy is the treatment of choice but is frequently associated to local complications. We investigated the association of chlorambucil and rituximab as first-line treatment for primary OALs. Nine consecutive, newly diagnosed OALs patients (eight with a EMZL, one with a follicular lymphoma) with a median age of 78 years were treated with this combination. Eight patients were in stage I-A, and one was in stage IV-A; all patients had low LDH values. Eight patients (89%) obtained a complete remission and one a partial response. All completed the treatment without significant toxicities. After a median follow up of 25 months, all patients are alive; no progressions or late toxicities were observed. Rituximab in combination with chlorambucil proved to be a feasible option as first-line treatment for OALs because of its feasibility and the absence of toxicity and local sequelae.