The reverse cationic flotation using the starch as depressor of iron oxides is the most efficient upgrading process when is applied to the simple systems composed by hematite/magnetite and quartz. The fundamental studies performed with iron ore samples from different deposits over the world (Brazil, Russia, Mexico) confirmed the inefficiency of starch when the silica content in the concentrate is controlled by Fe/Mg-bearing minerals. The main approaches for solving these issues focused on using new collector formulations or new depressants. However, the alternative depressants tested inhibited flotation of quartz or were less efficient as iron oxide depressant. In this work, a comparison between new amidoamine collector with conventionally used etheramine and oleate collectors in the flotation of pure minerals and actual iron ore samples was performed. The electrophoretic mobility, contact angle and infrared spectroscopy measurements allowed to deduce the hindrance effect as main mechanism of selective adsorption of the amidoamine on the quartz surface compared to hematite and kaolinite. Molecular modelling studies revealed that this steric hindrance effect can be explained by the combination of the "shield" formed by the coordinating water molecules on the (001)-D2 hematite surface and the large volume of the amidoamine head group. The amidoamine tested as collector without use of a depressant showed excellent flotation selectivity allowing the total flotation of quartz from a mixture with hematite. High collector performance and selectivity were confirmed during reverse flotation of quartz using continuous flotation column (D = 500 mm; H = 4000 mm) and allowed to produce the iron concentrates with more than 60 per cent of iron from the rejected slimes samples of Vargem Grande 2 processing plant (Iron Quadrangle, MG, Brazil). The new collector allowed to develop flexible flotation flow sheets to process the iron ore with a complex gangue mineralogy and unlock the old altered tailings and slimes product as new resources