Clinical implications of acute injuries of the os peroneum have been described, with the recommendation in some cases being the excision of the bone fragments. We describe the spectrum of sonographic appearances associated with pain in the region of the os peroneum, document associated peroneal tendon pathology, and describe the use of sonography to direct and guide therapeutic and/or diagnostic injections. All sonographic examinations in our ultrasound database from Jan 1, 2001–Jan 30, 2007 with the words “os peroneum” were reviewed. Patients were cross-referenced in our radiology database to find relevant foot or ankle radiographs for correlation. There were 47 patients (18 men and 29 women, age range 16 to 83) referred for sonographic evaluation of lateral foot and/or ankle pain who had an os peroneum identified during the sonographic evaluation. Eighteen patients were referred specifically for targeted injection of the lateral ankle, including peroneal tendon sheath injections (N = 10), calcaneocuboid joint injections (N = 1), and injections around symptomatic os peroneum (N = 7). All 47 patients had tendinosis of the peroneus longus, in varying degrees of severity. Radiographs were available for correlation in 28 patients. The causes of lateral ankle pain with a co-existent os peroneum are multifactorial and may not directly relate to the presence of an os peroneum. Ultrasound can be of value in separating out the specific etiology for pain, as well as provide a method for problem solving by the performance of targeted diagnostic or therapeutic injections in the lateral ankle.