PurposeAnaplastic thyroid carcinoma (ATC) is an orphan disease with a fatal outcome. Surgery to the primary tumor in metastatic ATC is controversial. Determination of specific surgical techniques may help facilitate local control and, hence, beneficial overall and disease-specific survival.MethodsUsing individualized patient data derived from our systematic review of literature and our single center study (n= 123), conducting a Surveillance, Epidemiology, and End Results register (SEER)-based study (n= 617) we evaluated surgery, its combination with systemic and local therapies in metastatic ATC.ResultsPooled cohort study showed surgery (p< 0.001), RT ≥ 30 Gy (p< 0.001), ChT (p< 0.001) and multimodal treatment (p= 0.014) to result in improved OS univariately. In the multivariate analysis, surgery (1.997 [1.162–3.433],p= 0.012) and RT ≥ 30 Gy (1.877 [1.232–2.843],p= 0.012) were independent predictors for OS. In SEER-based study of patients undergoing any tumor-directed treatment (n= 445) total thyroidectomy (p= 0.031), administration of ChT (p= 0.007), RT (p< 0.001), combination of surgery and RT ± ChT (p< 0.001) and multimodal treatment (p< 0.001) correlated with an improved DSS univariately. On the multivariate analysis, debulking surgery was an independent predictor for a worse outcome (HR 0.535, 95%CI 0.332–0.862,p= 0.010), whereas RT administration correlated with a longer DSS (HR 2.316, 95%CI 1.362–3.939, p = 0.002). Among operated patients from SEER register total thyroidectomy (p= 0.031), ChT (p= 0.007), RT (p< 0.001), combination of surgery and RT ± ChT (p< 0.001) and multimodal treatment (p< 0.001) correlated with an improved DSS in the univariate analysis, whereas debulking surgery was inversely correlated with the DSS (p< 0.001). On the multivariate analysis, debulking surgery was an independent predictor for a worse DSS (HR 0.535, 95%CI 0.332–0.862,p= 0.010), whilst RT administration correlated with a longer DSS (HR 2.316, 95%CI 1.362–3.939,p= 0.002).ConclusionsSurgery to the primary tumor with the aim of R0/R1 resection, but not debulking, is associated with a significant OS and DSS benefit even in systemically metastasized disease.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00432-022-04223-7.