Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) have traditionally been considered as two distinct entities. However, there are rare reports of patients that, over time, develop both diseases. It remains unresolved whether the origin of the two diseases is from the same clone. In this study, we attempted to retrospectively investigate the clinical and molecular aspects of patients who developed both lymphomas. The rearranged immunoglobulin heavy-chain variable region genes from both diagnoses were compared to each other. Twenty-six patients presented with both diagnoses. Twelve had HL as the primary disorder (" HL first" group) and the majority of these (75%) presented with aggressive lymphoma as the second lymphoma. In contrast, in the 11 patients for whom NHL was the primary disorder (" NHL first" group), this was usually (82%) of low-grade histology. Three patients were diagnosed concurrently with both diseases. Mean age at first diagnosis was higher (p = 0.037) in the NHL first group (56.1 years) than in the HL first group (40 years). Mean time between diagnoses was longer (p = 0.026) in the HL first group (9 years) than in the NHL first group (5 years). For 11 patients, diagnostic samples were available for molecular analyses from both diagnoses of HL and NHL. In 6 of these 11 patients, gene rearrangement studies were informative. No patient had the same gene rearrangement identified in both diseases. It seems that development of HL and NHL in one patient, at different time points, reflects, in many cases, separate biologic diseases.