A 52-year-old woman with overlap syndrome and interstitial pneumonia underwent immunosuppressive therapy and she was suspected to suffer from pulmonary aspergillosis. Oral voriconazole was initiated, and a rapid elevation of alkaline phosphatase (ALP) occurred after 4 weeks. After 2 months, the patient presented diffuse pain in bilateral skeletal regions, and bone scintigraphy revealed bilateral multiple areas of increased radiotracer uptake. We suspected the skeletal involvement as voriconazole-induced periostitis. Actually, the plasma fluoride level was increased. Voriconazole was replaced with itraconazole, and after 3 weeks, the patient stopped complaining of bone pain concomitant with the decrease in ALP. Voriconazole-induced periostitis is a rare condition but had previously been reported in solid organ or patients with bone marrow transplant who received a long-term voriconazole therapy. Our present case is distinctive of previous ones, because it occurred in a patient with connective tissue disease which had its rapid progression.