Rationale:In this case, the tumor cells were epithelioid, with translucent cytoplasm, well-defined cell borders, moderate size, rounded or ovoid nuclei, and small nucleoli visible. Based on this morphological feature, we first considered clear cell carcinoma, but the epithelial-related immunohistochemical results don't support the diagnosis. Ultimately, based on lymphoma-associated immunohistochemical results and gene rearrangement assays, the final diagnosis of a clear cell variant of DLBCL. Therefore, clinicians and pathologists are reminded that DLBCL with clear cell morphology is rare.Patient concerns:A case of a 44-year-old patient who presented with a 1-year's history of an oral tumor that had recently increased in size. Computed tomography (CT) showed an osteolytic lesion with soft tissue density in the right body of mandible with bone destruction in the cortical plates on both buccal and lingual sides.Test results: Immunohistochemistry include vimentin, LCA, CD10, CD20, CD38, B-cell lymphoma (Bcl)-2, multiple myeloma oncogene (MUC)-1, CD79a were strongly expressed, while the tissue was negative for the rest of epithelium and other mesenchymal antibodies. Detection of Ig and TCR gene arrangements showing the presence of B-cell monoclonal rearrangement (DH7-JH) in the tumor.Patient concerns:A case of a 44-year-old patient who presented with a 1-year's history of an oral tumor that had recently increased in size. Computed tomography (CT) showed an osteolytic lesion with soft tissue density in the right body of mandible with bone destruction in the cortical plates on both buccal and lingual sides.Test results: Immunohistochemistry include vimentin, LCA, CD10, CD20, CD38, B-cell lymphoma (Bcl)-2, multiple myeloma oncogene (MUC)-1, CD79a were strongly expressed, while the tissue was negative for the rest of epithelium and other mesenchymal antibodies. Detection of Ig and TCR gene arrangements showing the presence of B-cell monoclonal rearrangement (DH7-JH) in the tumor.Diagnosis:The final diagnosis was germinal center B cell-like (GCB) diffuse large B lymphoma of clear cell type.Interventions:The patient was treated with chemotherapy.Outcomes:The patient was undergoing chemotherapy and has been followed up for over 1 year.Lessons:Diffuse large B-cell lymphoma with clear cell morphology is a rare tumor, and its diagnosis mainly relies on pathological findings, immunohistochemistry, gene rearrangement.