Light and electron microscopic investigations and studies of the resorption ability in vitro of giant cells were done in two patients with giant cell osteolytic lesions of metatarsal bone. Giant cells harvested from both patients were similar in morphologic features and ability to resorb dentin. After other diagnoses of osteolytic lesions of metatarsal bone were ruled out, one lesion was considered a giant cell reparative granuloma and the other a true giant cell tumor of bone. Clinical, radiologic, ultrastructural, functional studies, and data in the literature, indicated that giant cell reparative granuloma only can be differentiated from giant cell tumor by younger age at diagnosis and the occurrence of giant cell clusters. All other features (cortical erosion, high rate of recurrence, hemorrhage areas, predominant intercellular collagenous substance) are characteristic of both lesions. If these two giant cell lesions are different entities, more accurate means are needed to distinguish them.