Genetic control of fatty acid composition in grain-fed beef calves was evaluated when the fatty acids are measured on a percentage of lipid basis and on a mg of fatty acid / g of beef basis. Fatty acids of concern for human health (e.g. 14:0, 16:0, 16:1, 18:0, and 18:1) show evidence of having genetic control. Heritability estimates for these five fatty acids indicate stronger genetic control when fatty acid concentrations are expressed on a percentage of lipid basis (h2 = 0.20 to 0.49) than when expressed on a mg of fatty acid / g of beef basis (h2 = 0.12 to 0.27). However, there may be some concern that selection for a healthier fatty acid composition may come through an overall decrease of lipid within the beef. This would have significant consequences for production of high quality beef in the U.S. Our goal was to identify tools which will allow for selection of a healthier fatty acid profile with similar or increased lipid within beef. The results of this study indicate that a selection scheme based on fatty acids expressed on a percentage of lipid basis with maintenance of lipid concentration as a selection goal would be the most likely selection scheme to utilize for improving the healthfulness of U.S. beef.