We describe a case of classic Kaposi's sarcoma (KS) in an Italian HIV-negative patient, with bone involvement and progression to anaplastic histotype. At the age of 22, violaceous patches of KS appeared on his feet. At the age of 50, he noted the appearance of a violaceous firm nodule on his right wrist. The lesions grew rapidly and became ulcerated. Radiotherapy led to a complete remission of symptoms. At the age of 55, a subcutaneous nodule developed on the proximal third of the right forearm associated with a wide painful edema of the right forearm and the proximal third of the right arm. The nodule enlarged rapidly, and an X-ray of the right forearm revealed the presence of a large osteolytic area of the ulna. A biopsy specimen from the right ulna showed bone erosion by a mesenchymal neoplasia with a high degree of malignancy. The right arm was amputated, and histologic examination of the surgical material confirmed the diagnosis of undifferentiated spindle-cell malignant neoplasia strongly positive for factor-VII-related antigen and CD34 antigen. Three years after surgical treatment, no recurrences have been observed.