PurposeNon-Hodgkin lymphoma (NHL) sometimes occurs in soft tissue (referred to as soft tissue lymphoma or soft tissue NHL), often mimicking soft tissue tumors. Despite some clinical indicators, accurate diagnosis of soft tissue NHL before biopsy remains challenging. We investigated the diagnostic value of serum soluble interleukin-2 receptor (sIL-2R) levels and magnetic resonance imaging (MRI) as an initial tool to assess the likelihood of soft tissue NHL. MethodsWe analyzed 36 cases of pathologically proven soft tissue NHL initially suspected as soft tissue tumors alongside 48 control cases of soft tissue sarcoma or carcinoma. Patient medical charts and MRI scans were retrospectively reviewed and statistically analyzed, focusing on assessing the diagnostic efficacy of soft tissue NHL. ResultsThe diagnostic accuracy of soft tissue NHL combining the appearance of homogeneity on MRI (T2-weighted and/or short-time inversion recovery [STIR] images) and sIL-2R value (≧ 904 U/mL) yielded a sensitivity of 78 % and 86 %, and specificity of 83 % and 88 %, respectively. Meeting one or both criteria increased the sensitivity to a maximum of 92 %, albeit with a specificity of 71 %. When both criteria were met, sensitivity and specificity were 72 % and 100 %, respectively. ConclusionThe integrated approach of combining MRI and sIL-2R demonstrated excellent efficacy in predicting the diagnosis of soft tissue NHL, which was initially referred to as soft tissue tumor.