A 43-year-old woman presented with a nodular melanoma treated with wide excision, split skin graft, and sentinel node biopsy. At 2-year follow up, she was noted to have clinical recurrence at the excision site. FDG PET/CT demonstrated in-transit metastasis in her left thigh in addition to disease at the site of the sentinel node biopsy. Isolated limb infusion was performed with melphalan and dactinomycin. PET/CT at 5 weeks demonstrated resolution of the in-transit metastasis and the disease at the excision site. This report of PET/CT demonstrates the effectiveness of chemotherapy for malignant melanoma delivered by isolated limb infusion.