Objective To describe fatal cases of gestational trophoblastic neoplasia (GTN) over four decades and evaluate whether treatment was given according to the protocol and reveal possible implications for future management.Design Retrospective cohort study.Setting The Netherlands.Population Women who died from GTN from 1971 to 2011.Methods Records from the Dutch Central Registry for Hydatidiform Moles and the Working Party on Trophoblastic Disease were used to identify fatal cases of GTN.Main outcome measures Disease extent, risk classification, treatment regimens and cause of death.Results Twenty-six women died from GTN. In five cases GTN developed after a hydatidiform mole and in 19 cases following term pregnancy. Half of the women died between 1971 and 1980, when women were not yet classified as having low-risk or highrisk disease and were therefore not yet treated accordingly. A major decline in the number of deaths was seen after the first decade, with a further decrease from 1981 to 2011. Early death occurred in nine women. In four of these women, death was treatment-related. Women who died more than 4 weeks after the start of treatment mostly died from metastatic tumour (n = 14).Conclusions The yearly number of women who died from GTN decreased considerably over the last four decades. Appropriate risk classification is essential to start optimal initial therapy and to prevent therapy resistance. Women with post-term choriocarcinoma represented a large proportion of the dead women and we propose that these women are considered as having high-risk disease.