Post-transplant lymphoproliferative disease (PTLD) is a potentially fatal side effect after solid-organ transplantation (SOT). For a study, researchers described the incidence and consequences of PTLD in a cohort of 5,365 SOT patients at two UK transplant centers over a 20-year period. PTLD developed in 142 of 5,365 individuals after a median follow-up of 7.7 years. The cumulative incidence was 18% five years after multivisceral transplant and 1–3% five years after the other SOT types. The cumulative incidence over a twenty-year period was 2%–3% after liver and heart transplantation and 10% after kidney transplantation. The median overall survival (OS) after SOT was 16 years, which was significantly lower than the age-adjusted UK population. There was a rather significant early mortality rate following PTLD diagnosis, and only those who survived two years regained a longer-term survival rate comparable to the non-PTLD SOT sample. First-line rituximab monotherapy was used in 66 patients with monomorphic PTLD, diffuse large B-cell lymphoma, while first-line rituximab plus chemotherapy was used in 24 patients. Although rituximab monotherapy did not appear to reduce OS, the number of patients dying from non-lymphoma causes before and after treatment was high with both treatments. An International Prognostic Index (IPI) of 3+ was revealed as the greatest pretreatment predictor associated with poor one-year OS in a multivariate study of all 90 monomorphic PTLD patients.