The minicolumn is generally considered an elementary unit of the neocortex in all mammalian brains. This essential building block has been affected by changes in the circuitry of the cortex during evolution. Researchers believe that enlargement of the cortical surface occurs through the addition of minicolumns rather than of single neurons. Therefore, minicolumns integrate cortical encephalization with organization. Despite these insights, few studies have analyzed the morphometry of the minicolumn to detect subtle but important differences among the brains of diverse mammals. The notion that minicolumns are essentially unchanged across species is challenged by strong evidence to the contrary. Because they are subject to species-specific variation, they can be used as a way to study evolutionary changes. Unfortunately, comparative studies are marred by a lack of standardized techniques, tissue preparation, cortical regions, or anatomical feature studied. However, recent advances in methodology enable standardized, quantified comparisons of minicolumn morphology.