Oncogenic osteomalacia (tumor-induced osteomalacia, TIO) is a rare paraneoplastic syndrome characterized by specific laboratory abnormalities (ipophosphoremia, hyperphosphaturia and low levels of 1,25 dihydroxyvitamin D). The symptoms, that may precede diagnosis of many years, is characterized by weakness, worsening myalgia, bone pain and impaired gait (waddling). The clinical picture shows a complete remission after removal of the tumor. The tumor is usually mesenchymal, benign, localized mainly in the limbs and face. Recent studies have identified the fibroblast growth factor-23 (FGF-23) as the substance responsible for the metabolic changes. Two other substances with similar characteristics to FGF-23 have been identified: MEPE (extra cellular matrix phosphoglycoprotein) and FRP4 (secreted fizzled-related protein 4), with possible implications in clinical manifestations. The case report is that of a 65-years-old patient known for osteomalacia oncogenes, followed by the Day-Hospital Orthopaedic Institute of Rheumatology G. Pini, Milan. In summer 2000, appearance of pain at the spine and rib-back injury. Laboratory tests show hyperphosphaturia and markedly reduced blood levels of phosphorus. On the basis of previous values a bone scintigraphy with octreotide was performed. These tests raise the suspicion of a phosphaturic mesenchymal tumor, that is confirmed by the biopsy performed at the level of the proximal third of the humerus. In 2005, the patient is surgically treated at the level of the two main sites of disease: right humerus and right femur. The postoperative course is uneventful and the rehabilitation program is performed with personal benefit. In March 2007, during a routine follow-up check, the patient reports pain in the humerus with evidence of illness in the radiographic images: a surgical resection is performed. During a rheumatologic follow-up in October 2007 the patient shows a normalization of phospho-calcium metabolism in the face of persistent severely reduced bone mass values. In April 2009, scintigraphic and radiographic loosening of the femoral stem. The patient is operated on for revision of the prosthesis stem. In 2010, radiographic evidence of progressive sinking of the femoral shaft, surgically treated with revision of the prosthetic implant; the patient is currently admitted to the Institute rehabilitation center for the regular postoperative course.