Introduction: The aim of this study was to investigate the basis for a differential diagnosis of lymph node tuberculosis and histiocytic necrotizing lymphadenitis. Methodology: This study selected 85 cases of lymph node tuberculosis (Group A patients) and 26 cases of histiocytic necrotizing lymphadenitis (Group B patients). The clinical and pathology features on both groups were analysed. Results: The Group A patients were older than the Group B patients (t = 5.233, P < 0.01); The Group B patients had less tuberculosis exposure history (x2 = 4.279, P < 0.01), and a higher frequency of tenderness (χ2 = 8.109, P < 0.01) and fever (x2 = 31.923, P < 0.01). The Group A patient group had a higher WBC level (t = 2.980, P < 0.01) and lower serum ALB (t = 5.508, P < 0.01); As seen through ultrasound imaging, Group B patients had more clear boundaries (70.59%), higher low-echo rates (82.36%) and low calcification rates (0%), Group A patients for whom these rates was 25.76%, 40.91% and 25.76% respectively. In terms of pathology data, the main manifestations of Group A patients were granulomatous inflammation with caseous necrosis, multinuclear giant cell reaction, and in some cases, acid-fast bacilli smears (+). In Group B patients, there were instances of coagulative necrosis surrounded by foam-like tissue cells without neutrophil infiltration. Conclusion: We found that the epidemiological history, clinical symptoms, laboratory examinations, ultrasound imaging and changes in pathology are very important for the identification of lymph node tuberculosis and histiocytic necrotizing lymphadenitis.