Patients who are immunodeficient or immunosuppressed are at risk of developing lymphoproliferative disorder (LPD). Methotrexate (MTX) is an iatrogenic cause of LPD. However, the occurrence of MTX-related LPD causing osteonecrosis of the jaw (ONJ) has rarely been reported. We report a series of three cases of MTX-related LPD in patients with longstanding rheumatoid arthritis who presented with ONJ. A 74-year-old man with rheumatoid arthritis (RA) had received treatment with MTX for seven years before presenting with ONJ and submental lymphadenopathy following dental extraction. The second patient was a 79-year-old woman who had been treated for 21 years with MTX and who presented with ONJ. The third patient in our series was a 67-year-old man who had been treated with MTX for more than 15 years. In all three cases, biopsy, histology, and immunohistochemistry using a panel of lymphoid markers (EBV, CD79a, CD20, PAX-5, CD3, and CD30) resulted in the diagnosis of EBV driven T-cell, B-cell, and Hodgkin-like LPD. All three patients recovered following cessation of MTX and surgical debridement. Although LPD as a cause of ONJ is rare, due to the rise in immunodeficiency disorders and immunosuppressive treatments, the prevalence of this condition may be expected to increase. For this reason, clinicians should be aware of the diagnosis. As this case series has shown, biopsy and diagnostic immunohistochemistry will ensure the correct diagnosis. Because the diagnostic approach used in this case series will distinguish MTX-related LPD from the more familiar condition of Medication-related osteonecrosis of the jaw.