Malignant transformation of fibrous dysplasia is very rare and has not been previously described in patients with McCune-Albright syndrome in the absence of radiation treatment during gestation. Here, we report a 38-year-old pregnant woman with McCune-Albright syndrome and acromegaly accompanied by osteosarcoma. The patient was in the 6th week of pregnancy, when she visited our hospital. She had multiple fibrous dysplasia, skin pigmentation, and acromegaly. The markedly high bone turnover rate during pregnancy tended to decrease after a normal delivery. Fibrous dysplasia of the lower jaw rapidly increased in the 37th week of pregnancy, and the tumor was surgically resected after delivery. Pathological examination of the resected tumor revealed fibrous dysplasia admixed with osteosarcoma containing chondroblastic and osteoblastic tissue. We firstly reported a case of osteosarcoma in a patient with McCune-Albright syndrome, which rapidly progressed during pregnancy.