Primary melanoma of the female urethra is extremely rare. Treatment by surgery, radiation, and chemotherapy has been uniformly ineffective. We herein report on 2 patients with primary malignant melanoma of the urethra treated with immunotherapy and chemotherapy. The first patient died four years after the initial diagnosis, and the second died after two years. Chemo-immunotherapy may be considered as an additional, palliative form of treatment in the management of primary melanoma of the female urethra, but cystourethrectomy should be the initial form of treatment.