Background Non-Hodgkin's lymphoma (NHL) accounts for around 4% of new cancer cases annually. Bone marrow involvement is important for staging and management. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is used increasingly to identify this, in addition to bone marrow biopsy (BMB), which is seen as "gold" reference standard. Purpose To compare determination of bone marrow involvement by FDG PET/CT against BMB in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Material and Methods This was a retrospective study of patients with histologically confirmed NHL at a single UK cancer center undergoing pre-treatment FDG PET/CT and BMB between June 2010 and February 2013. Information was collected from patient notes, cancer registry, histological and imaging reports. Diagnostic accuracy of FDG PET/CT was determined, compared to BMB as the reference standard. Results Twenty-four patients with DLBCL and 12 with FL were included. Five DLBCL patients had bone marrow involvement on PET/CT; all were confirmed on BMB. Three FL patients had marrow involvement on PET/CT but not on BMB; one FL patient had positive BMB but negative PET/CT. Using BMB as the reference standard, the sensitivity and specificity of FDG PET/CT for detecting bone marrow involvement in DLBCL were 100% and 100%, respectively, and in FL were 0% and 72.7%, respectively. Conclusion FDG PET/CT is accurate for detection of bone marrow involvement in newly diagnosed DLBCL, but not FL. In DLBCL, positive FDG PET/CT may negate the need for routine BMB, although BMB in addition or combination may be appropriate if this would influence management or prognosis.