Introduction: The use of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scanning for baseline staging and assessment of treatment response for higher grade lymphomas is considered to be the standard of care. Evaluation of lymphomatous bone marrow infiltration on 18F-FDG PET can usually distinguish between normal regenerating marrow following chemotherapy by a characteristic pattern of uptake. Case Presentation: Here we report the case of a 51-year-old Caucasian woman with mixed low- and high-grade lymphoma with biopsy confirmed marrow infiltration. An interim post-three cycle chemotherapy 18F-FDG PET scan revealed apparent progression of marrow disease. Subsequent investigations were performed including bone marrow biopsies, repeat 18F-FDG PET scanning and a white cell scan. These revealed the interim 18F-FDG PET scan appearance was due to a highly unusual pattern of scattered islands of regenerating normal marrow, rather than progressive lymphoma. Conclusions: Our case report highlights that apparent severe bone marrow abnormalities on 18F-FDG PET scans in lymphoma patients treated with chemotherapy are not always due to disease. Clinicians should retain a high index of suspicion for benign causes when 18F-FDG PET scan results appear incongruent with clinical response.