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Wheat (Triticum aestivum L.) is a primary staple cereal and significant source of mineral nutrients in human diets. Therefore, increasing concen - tration of the essential mineral, Zn, and decreas - ing concentration of the toxic mineral, Cd, could significantly improve human health. Because plant mechanisms for uptake and translocation of Cd and Zn are related, we assessed both Cd and Zn concentration to evaluate their indepen - dence in hard winter wheat germplasm. Grain Cd concentrations of some genotypes grown in Nebraska trials were above the Codex guidance level (0.2 mg kg -1 ), and highly repeatable dif - ferences in grain Cd were found between pairs of low and moderate-Cd commercial cultivars. Grain Cd concentration was predicted by Cd concentration in aboveground plant tissues at anthesis. However, grain Zn concentration was not predicted by Zn concentration in aboveg - round plant tissues. Genome-wide associa- tion scans using high-density single nucleotide polymorphism (SNp) markers identified Cd- associated SNps on 5AL in a region homoeolo - gous to the Cdu1 locus on 5BL in durum wheat (Triticum turgidum L. var. durum Desf.). Genetic regulation of grain cadmium concentration in bread wheat may be more complex than in durum wheat because epistatic interactions between SNp markers were identified, and SN p marker haplotypes were imperfect predictors of grain Cd phenotype. The SN p marker asso - ciations with Zn concentration were weak and inconsistent across trials, and Zn concentration was independent of 5AL markers. The inde - pendent genetic regulation of grain Cd and Zn concentrations indicates that breeding low Cd hard winter wheat genotypes without reducing Zn concentration has high potential for success.