Comminution is an essential step in processing itabirite ores, given the need to liberate silica and other contaminants from the iron minerals for downstream concentration and then pellet feed production. In general, these ores in Brazil are not particularly hard to crush and grind, but both capital (CAPEx) and operating (OPEx) expenditures in this stage of preparation can be critical for the project, in particular due to uncertainties in iron ore prices. Several circuits have been designed and are in operation for this type of ore in Brazil; however, it is not yet clear which technologies are more cost-effective and in which configuration they should be applied. This work critically analyzes four comminution circuits for an undisclosed case study. For these circuits, CAPEx, OPEx, and some environmental sustainability indices, as well as qualitative technical criteria, were used in the comparisons. This work concludes that two of these process routes, especially those based on more energy-efficient technologies (and one of these still rarely explored even at bench-scale), have demonstrated to be very attractive from multiple standpoints.