Pathological fractures have a high incidence in musculo-skeletal oncology, and localization in long bone causes severe pain, disability and poor quality of life. The aim of this retrospective case series is to evaluate the clinical results, in particular regarding the quality of life, in patients affected by lower long bone pathological fractures surgically treated. We analyzed 93 patients with pathological fractures of tibia and femur surgically treated in our Orthopaedic Department and followed up for at least 3 years or until their death. Intramedullary nailing or endoprosthetic reconstruction for pathologic fractures located in the metadiaphyseal and diaphyseal or proximal regions in advanced-stage cancer patients are suitable methods for a stable fixation or reconstruction. These approaches guarantee a good mechanical stability, a faster mobilization, a better control of pain with an overall improvement in quality of life in all patients, confirmed also by the trend of the ECOG performance status and QOL-ACD.