Complete follow-up for 4 to 27 years was achieved for virtually all 249 patients with medullary thyroid carcinoma (MTC) diagnosed in Sweden in a 23-year period. Tumor specimens from 241 patients were re-examined with regard to calcitonin immunoreactivity, amyloid content, argyrophil reaction, tumor capsule condition, and nuclear DNA content. In univariate analyses, these factors, with the exception of the argyrophil reaction, were strong predictors of survival. There were twofold-to-threefold differences in hazard rate between patients with a high (greater than 50%) and low (less than 10%) frequency of calcitonin-immunoreactive tumor cells, between those with amyloid-containing and amyloid-free tumors, and between those with an intact and a nonintact tumor capsule. Calcitonin immunoreactivity and the amyloid content also provided prognostic information in multivariate analyses that adjusted for all the other factors mentioned above and in the full multivariate model, which in addition considered age, sex, heredity, stage of the disease, tumor size, and treatment. The strong prognostic capacity of the nuclear DNA content found in univariate analyses became considerably weaker when other morphologic characteristics were considered.