Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, which leads to deranged bone turnover. TIO is usually associated with benign mesenchymal tumors, although it has also been reported in malignant tumors. We report the case of a 56-year-old individual who presented with a long clinical course of hypophosphatemia, weakness, and kyphosis, associated with a tumor in the foot. After several years, this lesion exhibited malignant behavior and was diagnosed as a high-grade sarcoma. To date, this case is among the 10 reported cases in the literature of a mesenchymal tumor associated with TIO undergoing malignant transformation. This report underscores the importance of a comprehensive evaluation of patients with unexplained hypophosphatemia, and highlights the need for diligent follow-up to detect possible malignant transformation of the underlying tumor. Clinicians should consider TIO in the differential diagnosis of hypophosphatemia, and promptly investigate for the presence of an underlying tumor, as early detection may improve the patient's prognosis.