IntroductionThe incidence of neuroendocrine neoplasms (NENs) seems to increase worldwide. However, long-term, population-based data that consider differentiation levels are sparse.ObjectiveTo evaluate the incidence trend of lung and gastroenteropancreatic (GEP) NENs according to the latest International Agency for Research on Cancer/World Health Organization classification over a 41-year time period in two Swiss regions.MethodsAll cases of lung and GEP NENs recorded in the Vaud and Neuchâtel Cancer Registries from 1976–2016 were included. NENs were stratified into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Changes in annual age-standardized incidence rates were calculated for lung and GEP NETs and NECs by sex.ResultsThere were 4141 patients diagnosed with NENs, of which 65% were men. The incidence of lung NETs did not reveal any statistically significant trend in men, but increased in women by 4.9%/year between 1976–2016. The incidence of lung NECs in men decreased significantly by 2.6%/year from 1985–2016 whereas the incidence of lung NECs in women increased significantly between 1976–1998 by 6%/year. For GEP NETs, a steady annual increase in incidence occurred between 1976–2016 with a magnitude of 1.7% in men and 1.3% in women. No trend in incidence of GEP NECs was found for both sexes.ConclusionsThe incidence trends of lung NECs in men and women parallel changes in smoking prevalence in the population whereas causes of the increase in incidence of GEP NETs are not fully understood. Our study supports the importance of evaluating the epidemiology of NENs by their differentiation level.