BackgroundIn diffuse large B-cell lymphoma (DLBCL), bone marrow involvement (BMI) has an important clinical implication as a component of staging and International Prognostic Index (IPI). MethodsThis study aimed to determine whether molecular analysis of immunoglobulin heavy chain (IgH) genes and PET/CT could overcome the limitation of de ning morphologic bone marrow involvement by trephination biopsy and could increase the diagnostic accuracy or prognostic prediction. 94 de novo patients with DLBCL underwent PET/CT, polymerase chain reaction (PCR) test for detection of IgH gene rearrangement, and unilateral BM trephination at diagnosis. Results9 patients (9.6%) were con rmed to present morphologic BMI (mBMI) based on trephination biopsy. On the other hands, 21 patients (22.3%) were con rmed to have IgH clonality (IgH BMI), while 16 (17.0%) were classi ed with BMI based on the assessment of PET/CT (PET BMI). Each IgH rearrangement PCR and PET/CT showed the high negative predict value of detecting the BMI. However, the combined assessment of IgH rearrangement and PET/CT could increase a diagnostic accuracy and speci city with 87.2% and 97.0%, respectively. The survival outcome of patients with double positive PET BMI and IgH BMI was signi cantly worse than that with either single positive PET BMI or IgH BMI, and even less than patients with neither PET BMI nor IgH BMI. (3-year PFS: 50.0% vs 75.4% vs 97.9%, p = 0.007, 3-year OS: 50.0% vs 75.6% vs 80.1%, p = 0.035, respectively). ConclusionThis study suggested that the combined evaluation of PET/CT and IgH rearrangement could give additional information of predicting therapeutic outcomes in patients with negative morphologic BMI as an important part of the prognosis.