Background The objective of this study was to develop a core collection of Triticum and Aegilops species as a resource for the identification and characterization of wheat lines with preventive activity against chronic diseases. Given that cancer is the leading cause of mortality in the world and shares risk factors with obesity, type-2 diabetes, and cardiovascular disease, and given that wheat has been reported to protect against these diseases, the core collection was developed based on cancer prevalence. Methods The Germplasm Resources Information Network (GRIN) database was used to identify Triticum and Aegilops species grown in regions of the world that vary in cancer prevalence based on the International Agency for Cancer Research GLOBOCAN world map of cancer statistics (2008). Cancer incidence data drove variety selection with secondary consideration of ploidy, center of origin, and climate. Results Analysis indicated that the geographic regions from which wheat is considered to have originated have a lower incidence of cancer than other geographic regions (P <0.01), so wheat lines from countries that comprise the ‘Fertile Crescent’ were highly represented in the core collection. A total of 188 lines were selected from 62,571 accessions maintained by GRIN. The accessions identified comprised two genera and 14 taxa of 10 species within 19 groups from 82 countries. The core collection is comprised of 153 spring, 25 winter, and five facultative selections of wheat. Conclusions A diverse core collection of wheat germplasm has been established from a range of regions worldwide. This core collection will be used to identify wheat lines with activity against chronic diseases using anticancer activity as a screening tool.