Hepatitis C-associated osteosclerosis (HCAO) is an uncommon condition characterized by increased bone density, skeletal pain and elevated bone formation markers. Since 1992, only 17 cases have been reported. We herein describe the case of a 61-year-old woman affected by severe pain involving the lower limbs. The laboratory data showed an elevated serum alkaline phosphatase level, and the patient was found to be seropositive for hepatitis C virus infection. In addition, an X-ray skeleton survey showed marked cortical thickening of both femurs and tibias, and a whole-body bone scan revealed an increased cortical radionuclide uptake in the involved bones. These findings were consistent with a diagnosis of HCAO. In this report, we discuss the patient's clinical course over 16 years and, for the first time, show a normalized radioisotope uptake on bone scanning 10 years after the diagnosis.