Osteolysis of the skull is fairly common. The clinical presentation and results of laboratory or imaging tests may suggest a benign or a malignant disease. However, histology is the only means of obtaining a definitive diagnosis and should therefore be performed at the slightest doubt. We report the case of a 58-year-old man who presented with a recent painless lump in the right temporoparietal region. Laboratory tests were normal. Brain imaging studies and total body radionuclide scanning showed no other lesions. However, the heterogeneous and aggressive appearance of the skull lesion prompted a surgical biopsy, which showed osteoblastic osteosarcoma. Chemotherapy and radiation therapy were given after complete excision of the tumor.