This chapter reviews the epidemiology, indications for surgery, and surgical treatment modalities for metastatic lesions of the femoral diaphysis. Specific attention is paid to surgical metastatectomy, which is generally supported with a goal of negative margins in select patients with renal cell carcinoma, papillary thyroid carcinoma, and some breast cancers with later osseous metastasis, particularly those with solitary or oligometastatic disease with a longer predicted survival. Patients with other malignancies that are relatively radio- or chemo-resistant and with longer predicted survival may also potentially benefit. When metastatectomy is performed, the most common methods of reconstruction include intercalary endoprosthesis and allograft reconstruction. For those patients not undergoing resection, intramedullary rod fixation is the most utilized surgical technique. We conclude the chapter with a detailed description of the authors’ preferred surgical technique for surgical metastatectomy with cemented intercalary prosthetic reconstruction.