BACKGROUND Anaplastic thyroid cancer (ATC) is an aggressive, rare malignancy associated with rapid growth and metastasis, and a very poor prognosis. We investigated the clinical characteristics, survival outcomes and independent prognostic factors associated with anaplastic thyroid cancer. AIM To assess to what extent the interaction between age and tumor stage affects mortality. METHODS A total of 622 patients diagnosed with anaplastic thyroid cancer, between 2010 and 2017 were enrolled in our study by retrieving data from the Surveillance, Epidemiology and End Results (SEER) database. We analyzed demographics, clinical characteristics, overall mortality (OM) and cancer specific mortality (CSM) of ATC. Variables with a P value < 0.1 were incorporated into the multivariate cox model to determine the independent prognostic factors. Furthermore, we analyzed the interaction between age and tumor stage on mortality. RESULTS In the multivariate analyses, the divorced/separated population had a lower OM [hazard ratio (HR) = 0.63, 95%CI: 0.42-0.94, P < 0.05] and CSM (HR = 0.61, 95%CI: 0.40-0.92, P < 0.05). OM was higher in tumors with direct extension only (HR = 6.26, 95%CI: 1.29-30.42, P < 0.05) and tumors with distant spread (HR = 5.73, 95%CI: 1.34-24.51, P < 0.05). CSM was also higher in tumors with direct extension (HR = 5.05, 95%CI: 1.05-24.19, P < 0.05) and tumors with distant spread (HR = 4.57, 95%CI: 1.08-19.29, P < 0.05). Mortality was not adversely affected by lymph node involvement. OM was lower in patients who received radiation (HR = 0.66, 95%CI: 0.53-0.83, P < 0.01), chemotherapy (HR = 0.63, 95%CI: 0.50-0.79, P < 0.01) or surgery (HR = 0.53, 95%CI: 0.43-0.66, P < 0.01). CSM was also lower in patient who received radiation (HR = 0.64, 95%CI: 0.51-0.81, P < 0.01), chemotherapy (HR = 0.62, 95%CI: 0.50-0.78, P < 0.01) or surgery (HR = 0.51, 95%CI: 0.41-0.63, P < 0.01). There was no significant interaction between age and tumor stage that affected mortality. CONCLUSION In this large US SEER database retrospective study, we found the mortality to be higher in advanced stage tumors with direct extension and distant metastasis. However, patients who received aggressive therapy showed a better overall survival. The aim of our study is to emphasize the importance of detecting ATC at an early stage and provide aggressive therapy to these patients. Since advanced stage ATC is associated with a dismal prognosis, we emphasize the need for randomized control trials and development of novel therapies that will be used to treat ATC.