A 65-year-old woman diagnosed with a nodular melanoma on the right shoulder had a PET/CT scan 13 months later demonstrating a FDG-avid mass in the left masseter muscle, which was asymptomatic and not clinically evident. Pathologic analysis confirmed metastasis of melanoma. Further subcutaneous, intramuscular and bone metastases developed and the patient was treated with surgery and immunotherapy. The patient is in complete-remission with no evident metastases seen on PET/CT 2.5 years after treatment with adoptive cell therapy using tumor-infiltrating lymphocytes (TIL therapy). Asymptomatic skeletal muscle metastases identified with PET/CT can have therapeutic and prognostic implications and a PET/CT scan should be performed as a true whole-body scan.