Among patients with differentiated thyroid carcinoma (diffTCa), the rare hyperfunctioning or toxic TCa (ToxTCa) was diagnosed when scintigraphic hot thyroid areas were attributable only to diffTCa (diameter >1 cm by pathological examination) and/or total thyroidectomy failed to induce hypothyroidism. Of 924 cases of all TCa (papillary diffTCa 47.3%, follicular diffTCa 44.2%, others 8.5%), 19 had ToxTCa (2.1%, 15 of 19 follicular, 4 of 19 papillary, P = 0.008). These received a more intensive radioiodine therapy (average cumulated (131)I activities 21.8 vs. 15.2 GBq, P < 0.01). Five-year survival rates for ToxTCa (n = 19, 56%) and diffTCa (n = 545, 94.5%) differed [hazard ratio 4.8, 95% confidence interval (CI) 2.8-8.1, P = 0.001]. However, the differences were attenuated by matching ToxTCa and diffTCa (n = 57, 5-yr survival rate 74%) for age, sex, and histopathologic type (hazard ratio 2.1, 95% CI 1.13-3.9, P = 0.02). Correcting statistically for M(1) against M(0) stage distribution resulted in a further reduction of the hazard ratio (hazard ratio 1.8, 95% CI 0.93-3.48, P = 0.08). An M(1) stage is an important prognostic factor in ToxTCa patients. Thus, ToxTCa, treated with higher activities of (131)I, has a survival prognosis close to that of matched diffTCa cases, both groups consisting mainly (79%) of follicular subtypes.