Background: Extra-nodal diffuse large B-cell lymphoma (DLBCL) is an exceedingly uncommon disease. Case Presentation: Herein, we report a case of a 60-year-old male patient who presented with DLBCL of the left leg, and involving the gastrocnemius muscle. The patient received CHOP regimen-based neoadjuvant chemotherapy (i.e., six courses of cyclophosphamide, doxorubicin, vincristine, and prednisone), which reduced the tumor size to the point where complete resection became possible. Afterward, the tumor was completely resected. The tumor bed subsequently received conventional radiotherapy (i.e., 36 Gy/18 fractions). The patient is being followed up regularly and has remained disease-free for over 1.5 years. Conclusion: This case demonstrates that DLBCL is an aggressive malignancy but can be effectively managed with multi-modality treatment strategy.

Keywords: Diffuse large B-cell lymphoma, CHOP regimen, R-CHOP regimen, non-Hodgkins lymphoma, radiotherapy