Differentiation between benign fibrous dysplasia and malignant adamantinoma of the tibia is challenging because of the impact the diagnosis has on the choice of treatment (none or extensive surgery). The histologic and pathologic similarities of the lesions and the controversial relationship between fibrous dysplasia, osteofibrous dysplasia, and adamantinoma complicate the matter. We found a large overlap of histologic features in lesions considered either fibrous dysplasia or osteofibrous dysplasia on the basis of the radiologic findings. The purpose of this study was to determine the value of the plain radiograph of the lower leg in combination with clinical findings to differentiate the benign from the malignant condition. The clinical symptoms, radiographs, and histologic slides of 46 patients with fibrous dysplasia and 22 with adamantinoma in the tibia were reviewed retrospectively. In only one of 12 patients with radiologic or histologic characteristics of osteofibrous dysplasia were both radiologic and histologic criteria for the diagnosis present. A linear discriminant analysis was performed on six clinical (age, spontaneous pain, pain after trauma, swelling only, pain and swelling, and bowing deformity) and 25 radiologic signs. Fibrous dysplasia and its variant osteofibrous dysplasia could be identified correctly in 87% (40 of 46 patients) and adamantinoma in 95% (21 of 22 patients) by using the patient's age and four radiologic signs. When results from the discriminant analysis of a randomized subgroup of patients (32) were used on the other subgroup (36 patients), fibrous dysplasia was correctly identified in 84% (21 of 25) and adamantinoma in 82% (nine of 11). Fibrous dysplasia is more prevalent than adamantinoma in a young patient, when radiographs show a ground-glass appearance and anterior bowing and when there is no multilayered periosteal reaction and moth-eaten destruction. When radiologic signs and the patient's age are combined, fibrous dysplasia and adamantinoma can be discriminated in a high percentage of patients.