The authors have devised a new treatment regimen consisting of combination Adriamycin and hyperfractionated radiation therapy for the treatment of anaplastic giant and spindle cell carcinoma of the thyroid gland. The regimen consists of a once weekly administration of low-dose Adriamycin (doxorubicin) (10 mg/m2) and hyperfractionated radiation therapy. The radiation therapy is carried out with fractional dose of 160 rad per treatment twice a day for three days per week. The total tumor dose is 5760 rad delivered in 40 days. Since 1979, nine patients underwent the foregoing combination treatment regimen. Eight of nine achieved complete tumor regression in the primary treated area and six remained free of disease in the neck until time of death or last follow-up. There was no disproportionately enhanced normal tissue morbidity seen with this combined approach. If an effective systemic treatment regimen can be devised for anaplastic carcinoma of the thyroid, the present Adriamycin and hyperfractionated radiation therapy may be capable of achieving improved survival time.