Patients with inborn errors of immunity (IEI) have a higher risk of developing cancer, especially lymphoma. However, the molecular basis for IEI-related lymphoma is complex and remains elusive. Here, we perform an in-depth analysis of lymphoma genomes derived from 23 IEI patients. Our comprehensive genetic characterization of lymphomas derived from patients with rare genetic disorders expands our understanding of lymphomagenesis and provides new insights for targeted therapy.