Objective: The aim of this study is to comprehensively investigate the clinical manifestations, pathological diagnosis, differential diagnosis, and prognostic implications in patients with diffuse large B-cell lymphoma (DLBCL) manifesting as bone marrow invasion accompanied by peripheral blood counts. Method: A retrospective analysis was conducted on 16 patients diagnosed with DLBCL involving bone marrow and exhibiting peripheral blood abnormalities. Detailed clinical data, laboratory investigations, bone marrow biopsy hematoxylin and eosin (HE) sections, and immunohistochemical stains were compiled and analyzed. Results: Among the patients, B symptoms (11/16, 68.75%) and fatigue (9/16, 56.25%) were the most common symptoms. The diagnostic accuracy of bone marrow biopsy was 100%(16/16). The distribution pattern of abnormal cells in bone marrow biopsies was diffuse in 37.5%(6/16), interstitial in 31.25%(5/16), mixed in 18.75%(3/16), and nodular in 12.5%(2/16) of cases. The tumors originated from the germinal center in 12.5% (2/16) of cases and from non-germinal center sources in 87.5%(14/16). Fibrosis grades were distributed as follows: grade 0 in 1 case (1/16), grade 1 in 7 cases (7/16), and grade 2 in 8 cases (8/16).All 16 patients exhibited invasive disease progression, 3 fatalities ocuuring due to lack of treatment.1 patient unfortunately passed away six months after commencing R-CHOP and R-DHAP chemotherapy. Conclusion: This study offers a comprehensive insight into the clinical and pathological features of DLBCL infiltrating bone marrow with peripheral blood reduction, highlighting the importance of accurate diagnostic techniques and timely intervention in these patients.