The best staging system to employ for MALT lymphomas is still the subject of discussion. However, it is standard practice that patients presenting with MALT lymphomas should be evaluated in a similar manner to individuals with nodal lymphomas, the more common type of lymphoma that originates at sites within the lymphoid system. These procedures include a complete history and physical, blood tests, chest x rays, and bone marrow biopsy. This evaluation will permit the oncologist to determine if the disease is localized or if it has spread to other sites within the body.

In general, the prognosis for patients with MALT lymphomas is good, with overall five-year survival rates that are greater than 80%. The features that are most closely related to the outlook for newly diagnosed individual patients are: whether the primary site is in the stomach or is extra-gastric; if the disease has spread beyond the initial location; and whether the histologic evaluation of the initial tumor biopsies is consistent with a low-grade, slowly growing lesion, as compared to a high-grade lesion that is more rapidly growing. In general, the histologic grade is the most important feature, with high-grade lesions requiring the most aggressive treatment.

Treatment of MALT lymphomas differs from that of most lymphomas. In the most common type of MALT lymphomas—low-grade lesions originating in the stomach—treatment with antibiotics to eliminate H. pylori leads to complete remissions in the majority of patients. The effectiveness of this treatment is indistinguishable from surgery, chemotherapy, radiation therapy, or a combination of surgery with drugs or irradiation. Approximately one-third of patients in this group have evidence of disseminated disease, where lymphoma cells are detected at sites in addition to the gastric mucosa. The response of these patients to antibiotic treatment is not significantly different from that for individuals with localized disease. For both groups a complete remission is achieved in about 75% of patients, who remain, on average, free of disease for about 5 years.