Diffuse large B-cell lymphoma is the most common non-Hodgkin’s lymphoma. p63 is expressed in diffuse large B-cell lymphoma, which may be misdiagnosed as a p63-positive epithelial malignant tumor, especially when lymph node metastasis occurs. The study reported a patient with diffuse large B-cell lymphoma with respiratory symptoms as the first symptom. There is a high clinical suspicion of lung malignancy and lymph node metastasis. In the pathological diagnosis of right axillary lymph node biopsy, a positive p63 suggested squamous cell carcinoma, and the final diagnosis was diffuse large B-cell lymphoma after perfect immunohistochemical examination. Therefore, it is necessary to recognize p63-positive diffuse large B-cell lymphoma, which can decrease the possibility of misdiagnosis.