We present a case of a 65-year-old woman with a history of melanoma of the left foot who underwent tumor resection with inguinal lymph nodes dissection and received external beam radiation therapy. After some time, she developed nodular lesions in the same region that were confirmed to be due to involvement of the dermis. She was selected as a candidate for isolated limb perfusion procedure. The isolated limb perfusion was performed with the aid of radioguided monitoring of systemic leakage by injecting 99m Tc-labeled macroaggregated albumin, and whole-body acquisition was also performed, which confirmed compartmental localization of the tracer. Our case is the first one in which 99m Tc-labeled macroaggregated albumin injection has been used.