A cell line was established from undifferentiated giant cell carcinoma of the thyroid. The authors obtained cells from a 44-year-old patient admitted because of a rapidly growing anterior neck mass. The patient had significant leukocytosis and hypercalcemia shortly before her death. An autopsy revealed epidermoid metaplasia of the tumor cells. The cells (HTC/C3) had lost most of their differentiated functions. However, their thyroid nature was shown by peroxidase staining and by enzyme-linked immunostaining with Hashimoto patients' sera. The tumor extract was found to contain parathyroid (PTH)-like activity. Significant amounts of colony stimulating factor (CSF), which was further defined to be GM-CSF, and interleukin-1 alpha (IL-1 alpha) were detected in the conditioned media. Epidermal growth factor (EGF) binding to the HTC/C3 showed rich EGF receptors. Furthermore, the conditioned medium inhibited the binding of 125I-mEGF to HeLa cells, and transforming growth factor (TGF) was found repeatedly in the media.