The nuclear DNA content of 27 cases of primary bone tumors was determined by flow cytometry, using paraffin-embedded archival tissue, in order to investigate the appilicability of DNA analysis of differential diagnostic purposes. The series included 15 benign tumors (8 giant cell tumors, 4 fibrous dysplasias, 2 chondroblastomas, 1 osteoblastoma) and 12 malignant tumors (9 osteosarcomas, 2 malignant fibrous histiocytomas, 1 adamantinoma). Most of the benign tumors, except for one giant cell tumor (case No. 1), were diploid, whereas all malignant tumors were aneuploid. Histologically, a giant cell tumor (case No. 1) with an aneuploid. Histologically, a giant cell tumor (cases No. 1) with an aneuploid stemline showed a marked degree of stromal atypia and increased mitotic activity. The mean S-phase fraction (SPF) value of the benign tumors was 7.2, whereas 4 out of 7 giant cell tumors having an unimodal diploid pattern had higher SPF values (> 8.0). These cases showed a moderate degree of stromal cellular atypism. Among osteosarcomas case No. 24, which was primarily evaluated as an aggressive osteoblastoma, proved to be an aneuploid tumor. Six out of nine osteosarcoma patients died within 12 months after surgical excision. Thus, it appears that DNA analysis in primary bone tumors might contribute to increase the diagnostic accuracy, in addition to providing a predictive information about biologic behavior.