Plasmacytoid dendritic cell leukemia (pDCL) is a rapidly evolving disease, which frequently presents with skin lesions, particularly nodules and plaques with a typical reddish-brown or brown color. Treatment of pDCL is based on multiagent chemotherapy followed by allogeneic hematopoietic stem cell transplant, but skin lesions may be refractory to therapy. Here, we report on a 61-year-old patient affected by pDCL who first presented with multiple cutaneous nodules and plaques on the trunk. Lesions showed an excellent response to radiotherapy plus hyperthermia. Although this treatment did not avoid the systemic evolution of disease, it resolved skin lesions and prevented their relapse, thus representing a therapeutic option to be used in combination with chemotherapy regimens. The case presentation is followed by a general discussion with an emphasis on the diagnosis and treatment of this rare malignancy.