We report the case of a middle-aged patient with repeated attacks of regional migratory osteoporosis of the lower limbs, manifesting as severe pain and swelling of both joint and periarticular areas, and marked physical disability during a period of 2 1/2 years. After the therapeutic failure of conservative therapy (physical therapy, rehabilitation therapy, analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs)) and after the correct diagnosis was reached, pamidronate treatment was instituted. The results were a rapid, complete, and long-lasting remission of the symptoms and the renewal of the patient's previous activities. Intravenous biphosphates are proposed as a safe and promising therapy for regional migratory osteoporosis. To our knowledge, this is the first report of pamidronate treatment for this condition.