Patients with advanced malignant melanoma (MM) often do not receive satisfactory treatment. The present study reports the case of a 51-year-old female patient with stage IV MM of unknown primary. After undergoing immune checkpoint inhibitor therapy, the patient received multiple doses of hypofractionated radiotherapy (HFRT) for the left inguinal lymph node and single-fraction high-dose-rate brachytherapy for the left and right lung metastases. After combination treatment, the patient experienced almost complete remission of the inguinal target area, significant relief of pain and discomfort and an improved quality of life. The time of lung radiotherapy lesion control was 8 months. Meanwhile, the observed lesions (observation lesions 1, 2, 3 and 5) adjacent to the target lesion received lower doses of scattering (0.9-1.8 Gy) and the time of control for these lung observation lesions was 9 months. In addition, restarting targeted therapy after cessation of other treatments due to myelosuppression resulted in a progression-free survival time of 6 months. Nevertheless, the patient developed new metastases in the brain and abdomen. The present case report demonstrates that high-dose radiotherapy combined with immunotherapy may be effective for local lesions and that multiple doses of HFRT may be superior to single-fraction high-dose-rate brachytherapy for certain patients. Low-dose scattering also shows improvement for local lesions. Furthermore, restarting targeted therapy may be effective in the presence of target sites. Thus, the present case report provides a possible therapeutic option for the treatment of advanced melanoma.