Organ transplantations can lead to post-transplant lymphoproliferative disorders (PT-LPDs) as a result of immunosuppressive therapy. PT-LPDs clearly differ from non-Hodgkin's lymphomas occurring in immunocompetent patients, in terms of clinical presentation, pathological findings and treatment response. Several studies have tried to establish some prognostic factors but the small number of patients hinders the analysis. We studied 61 patients from two transplant centers who developed a PT-LPD after kidney (34 patients), heart (19 patients), lung (4 patients) or liver (3 patients) transplantation. Treatment consisted of modification of the immunosuppressive regimen, chemotherapy and/or monoclonal antibody infusions. Analyzing potential prognostic factors, we found that factors predictive of failure to achieve a complete remission were, in univariate analysis, a performance status (PS) > or =2 and negativity of the tumor for the Epstein-Barr virus (EBV), and in multivariate analysis, only the PS. Factors predictive of lower survival were, in univariate analysis, a PS > or =2, number of sites > 1, primary central nervous system (CNS) location, T-cell phenotype, monoclonality of the tumor, tumor negativity for EBV and chemotherapy as a first treatment; in multivariate analysis, only PS and the number of sites were statistically significant. The International Prognostic Index (IPI) failed to identify a patient subgroup with a lower survival or treatment response, whereas a simple index using PS and number of sites clearly identified three different groups. The median survival has not yet been reached in the lower-risk group, whereas it is 34 months in the intermediate-risk patients and 1 month in the high-risk group. Studies on larger cohorts of patients need to be performed to confirm these data.