We describe 2 patients with seropositive rheumatoid arthritis treated with methotrexate (MTX) who developed Hodgkin's disease (HD) and non-Hodgkin's lymphoma. Followup allowed a lymph node biopsy at 4 different time points in 1 patient and at 2 in the other. In the first patient, the steps included a long history of benign follicle hyperplasia, a polymorphic diffuse B cell lymphoproliferation, and finally HD unassociated with Epstein-Barr virus (EBV). In the second patient, a polymorphic diffuse lymphoproliferation was followed by a monomorphic large B cell lymphoproliferation associated with EBV. The cytogenetic analysis showed a monoclonal proliferation associated with the same chromosomal abnormalities found in 1 of the clones observed in the initial biopsy. These 2 cases illustrate the complexity of the role of MTX in the outbreak of such manifestations.