Estrogen receptors, progesterone receptors, and cathepsin D were determined in 10 patients with giant-cell bone tumor. Progesterone receptors were expressed in 5 of 10 patients tested, whereas low levels of estrogen receptors were found in 1 patient. Cathepsin D levels were elevated in 5 of 5 samples studied. High values of progesterone receptors correlated with low tumor grade. Cathepsin D levels correlated negatively with tumor grade but positively with local tumor expansion. Giant-cell bone tumor expressing progesterone receptors may manifest benign behavior. Cathepsin D may be involved in tumor expansion, possibly through its effect on bone resorption.