BACKGROUND: Among patients with well differentiated papillary thyroid carcinoma who generally have an excellent prognosis and a near-normal lifespan, there exist subsets of patients who have significant risk for morbidity and mortality from this disease. It is important to define the patterns of disease progression and the clinical outcome of such patients to develop effective surveillance and treatment strategies. Patients with recurrence after surgery and therapeutic administration of radioactive iodine (RAI) for papillary thyroid carcinoma represent one such subset of high-risk patients. METHODS: At the University of Texas M. D. Anderson Cancer Center, 65 patients with papillary thyroid carcinoma were diagnosed between 1970 and 1990. Their medical records were reviewed with particular attention to disease recurrence and outcome as well as RAI imaging and treatment. RESULTS: Following diagnosis and initial therapy, 19 patients died from thyroid carcinoma after a median of 64 months; 34 had no evidence of disease for a median of 112 months of available follow-up; and 7 are alive with disease 61 to 153 months after diagnosis. Cervical lymph node metastases were present in 41 patients and extrathyroidal or extranodal tumor invasion was seen in 25 patients at the time of initial surgery; distant metastases (lung, bone, brain, liver, and adrenal) developed later in 18 patients. RAI uptake by recurrent tumor deposits in the neck was seen most frequently in patients with no direct invasion of adjacent tissues but with recurrence limited to cervical lymphadenopathy; this group of patients was the most likely to become clinically and radiologically disease free. RAI generally did not concertrate in invasive cancers with extrathyroidal or extranodal extension in the neck; patients with this type of invasive carcinoma were also more likely to die from the disease. CONCLUSIONS: We suggest that among patients with recurrent papillary thyroid carcinoma, invasive cancers are less likely to concertrate RAI, whereas patients with disease confined to lymph nodes are more likely to have RAI-avid tumors and to benefit from RAI therapy.