It is desirable that noninvasive differential diagnosis takes place without lymph node biopsy for histiocytic necrotizing lymphadenitis (HNL) or malignant lymphoma (ML). In this study, we propose a novel scoring model for the differential diagnosis of these diseases using clinical information and clinical findings. We retrospectively analyzed the data from 15 HNL and 13 ML pediatric patients. First, a univariate analysis identified 14 clinical factors with significant differences. Second, a subsequent analysis using receiver operating characteristic (ROC) curve analysis identified three factors among them with area under the ROC curve values of >0.95: body temperature (°C), maximum lymph node size (cm), and serum β₂-microglobulin level (mg/L). Finally, the cut-off values of each of these three factors were determined and examined for the 28 cases. All 15 HNL cases were within 2–3 of the cut-off values among the three factors, no ML case was within two or more cut-off values. Thus, the diagnostic sensitivity and specificity of this novel scoring system were both 100%, indicating that clinical scoring with body temperature, maximum lymph node size, and β₂-microglobulin are useful for distinguishing between HNL and ML.