1. A series of eighty-five cases of giant-cell tumors of bone studied in the course of the last twenty years is reviewed. Comparative clinical, roentgenographic, pathological, and systematic histochemical studies have been carried out. 2. The clinical and pathological findings confirm the necessity of treating these tumors as an entity, because they are neoplastic processes capable of progressive growth, recur in a large percentage of cases, and, in 7 to 15 per cent of cases become transformed into sarcomata. They may produce metastases without visible malignant transformation. The so-called variants, which in general have a favorable prognosis, are easily distinguishable from true giant-cell tumors. 3. With the exception of a few rare cases showing a frankly malignant microscopic structure, there was no evident correlation between the histological appearance and the clinical and roentgenographic features. For this reason, grading of this neoplasm is now considered of little value. It is sufficient to establish a diagnosis of true giant-cell tumor to justify complete resection of the lesion. This diagnosis can be made by aspiration biopsy. 4. I believe that the giant cell derives from the mononuclear cell of the stroma and is thus of mesenchymal origin. I think that it is formed not only by agglutination and conglomeration of these cells, as is maintained by the majority of writers, but also by repeated division of the stromal-cell nuclei, without corresponding cytoplasmic division. This is probably accomplished by amitosis or nuclear segmentation, which has been observed in tissue cultures. 5. Systematic histochemical investigations of normal tissues, true giantcell tumors, and many bone lesions and extra-osseous lesions, which are characterized by the richness of multinucleated giant cells, were done. The giant cells in these tissues have a very similar histochemical behavior. A close physiological and histogenetic relationship is thus established between normal osteoclastic and chondroclastic giant cells and those of giant-cell tumor. 6. Giant cells are characterized by an abundance of acid phosphatase, betaglucuronidase, and succinic dehydrogenase; the absence of alkaline phosphatase; and the presence in their cytoplasm of non-glycogen carbohydrates, principally acid mucopolysaccharides, and complex lipids. The stromal cells of giant-cell tumors do not generally show enzymatic reactions, nor do they possess glycogen, mucopolysaccharides, or glycolipids in significant amounts. 7. Histochemical study is of no diagnostic value when differentiating the giant-cell tumor from its so-called variants.