BACKGROUND: Tumor marker doubling time (DT) has been proposed as a prognostic marker for various types of cancer. The present study analyzed the DT of the thyroid-specific tumor marker thyroglobulin (Tg), focusing on patients with progressive differentiated thyroid cancer (DTC). METHODS: A total of 144 Tg courses of 99 patients with progressive or recurrent DTC were included (median observation period 19 months, 3-11 Tg measurements per course) in this retrospective study. The distribution of Tg-DT was determined for both a highly sensitive assay (functional working range 0.03-3 ng/mL) and a routine assay. Tg-DT and other prognostic markers were used to perform uni- and multivariate statistical analyses for survival predictors. RESULTS: The median Tg-DT was 212 days (95% percentile: 49-961 days). No significant differences were observed between DT derived from Tg values in the very low range using a highly sensitive assay and DT calculated from Tg values measured by a conventional Tg assay. Multivariate analysis yielded no simple correlation between Tg-DT and survival rate, but the mortality risk of patients with a Tg-DT 14 months. Highly significant differences on survival rates were only observed in patients with a high tumor load (Tg >100 ng/mL). CONCLUSIONS: Tg-DT alone is not an independent survival predictor in all patients with progressive DTC; however, analyzing only patients with a high tumor load, we found highly significant differences in survival rates.