The incidence of lymphoproliferative disorders associated with methotrexate is rising in patients with rheumatoid arthritis. These disorders typically exhibit spontaneous tumor regression upon discontinuation of methotrexate therapy. Spinal lesions associated with these diseases are extremely rare. We present a case of systemic lupus erythematosus in which the patient developed lumbar spine lymphoproliferative disorders secondary to methotrexate therapy, which failed to regress despite discontinuation of the drug, ultimately leading to pathological fracture necessitating posterior spinal fixation. A 60-year-old woman had been diagnosed with systemic lupus erythematosus at the age of 55 years and had been taking prednisolone, hydroxychloroquine, and methotrexate. Throughout the course of her treatment, she experienced recurrent tumefaction and lymph node swelling in various locations. These masses and lymphadenopathy were believed to be potential complications of methotrexate-associated lymphoproliferative disorders, leading to the discontinuation of methotrexate. One month prior to cessation of methotrexate therapy, the patient presented to an orthopedic clinic with lower back pain, and T2-weighted magnetic resonance imaging revealed low signal intensity in the Th10 and L2 vertebrae, initially misdiagnosed as lumbar spinal stenosis. The patient was eventually referred to our department under suspicion of malignant pathology. Computed tomography identified a vertical fracture of the L2 vertebra, which, in conjunction with the imaging results, led to the diagnosis of pathological fracture secondary to methotrexate-associated lymphoproliferative disorder. Following admission to our department, bone biopsy and percutaneous pedicle screw fixation were performed one week later. Pathological examination confirmed the diagnosis of methotrexate-associated lymphoproliferative disorder. Given the possibility of pathological fracture in patients on methotrexate therapy experiencing severe back pain, additional imaging studies should be considered.