We hereby present a retrospective clinicopathological and immunohistochemical study of surgically resected primary gastrointestinal (GI) lymphoma with an analysis of parameters of potential prognostic relevance. From a larger series of 144 cases of primary GI lymphomas, we chose 61 cases with sufficient clinical follow-up (mean 60, range 1-219 months), classified either as extranodal marginal zone B-cell lymphoma of MALT type (MALT lymphoma) or diffuse large B-cell lymphoma (DLBCL), after having excluded other subtypes. In addition to conventional clinical and morphological parameters, the expression levels of Ki-67 (MIB-1), bcl-2 and p53 were evaluated for prognostic significance. Twenty-one (34.4%) cases were classified as pure low grade marginal zone B-cell lymphoma of MALT type, 12 (19.7%) cases as low grade MALT lymphoma with a high grade component (mixed type), and 28 (45.9%) cases as primary extranodal DLBCL. Most of the lymphomas (53/61; 86.9%) were localized in the stomach, 3 (4.9%) in the small bowel, 3 (4.9%) multifocal in both stomach and small intestine and 2 (3.3%) in the large bowel. MIB-1 expression in more than 30% of tumor cells was detected in 42 (68.6%), bcl-2 expression in 20 (32.8%) and p53 accumulation in more than 10% of neoplastic cells in 16 (26.2%) lymphomas. Both high Ki-67 expression and p53 accumulation were more prevalent in the DLBCL. 30 (49%) patients showed lymph node involvement at surgery, 14 (23%) patients suffered tumor recurrence, and 24 (38.5%) died during the follow-up period. Tumor recurrence occurred primarily in patients who had presented lymph node involvement (9/14, 64.3%). The 5-year survival rate was 66.1% for all patients. Important prognostic factors for overall survival were tumor stage (p < .004) and p53 accumulation (p < .05) in univariate analysis, and tumor stage in multivariate analysis (p < .001). Although p53 accumulation did not reach statistical significance in our small study group, it may be both important in the transformation of low grade MALT lymphoma and an indicator for aggressive behavior in high grade tumors.