We have previously reported on the efficacy of a modified International Prognostic Index (MIPI) in predicting the outcome of patients with primary gastric lymphoma. This prompted the retrospective analysis of a large series of patients with primary intestinal lymphoma (PIL) of both diffuse large B-cell (DLCL) and low-grade (extranodal marginal zone B-cell lymphoma, MZL) histology. Clinical records of 122 patients with localized primary intestinal lymphoma of MZL (n = 35) and DLCL (n = 87) histology, confirmed by an ad hoc expert panel of pathologists, were reviewed. Forty-nine patients were treated with single therapy, while 72 received combined-modality treatment, which included surgery followed by a short-term chemotherapy. MIPI was included in a multivariate prognostic analysis for overall survival (OS) and event-free survival (EFS). Sixty-five patients (75%) with DLCL and 22 with MZL (65%) achieved complete remission. After a median follow-up of 42 months (range 6-163 months), 5-year estimates of OS and EFS were 68% and 50% for DLCL and 65% and 26% for MZL. OS varied according to MIPI, from, respectively, 86% and 87% for DLCL and MZL patients with 0-1 risk factor to 50% and 32% for patients with > 1 risk factor (P = 0.01 and P = 0.02). Similar results were obtained for EFS. Cox regression analysis showed an unfavourable MIPI to be the only independent predictor of shorter EFS. This retrospective study shows that stage-MIPI can be a reliable prognostic indicator for PIL of both low-grade MZL and diffuse large B-cell histology, enabling the early identification of patients at higher risk of failure.