We report results of the first cytogenetic study of an osteoblastoma. Cells from the tumor were characterized by a three-way unbalanced translocation involving chromosomes 15, 17, and 20. As a consequence of the translocation, most of one chromosome 17 short arm appears to have been lost. This loss suggests the possibility that loss of 17p DNA sequences may be involved in early changes leading to neoplastic proliferation of osteoblasts.