When you walk down a museum hall full of Renaissance paintings, you can easily pick out the Italian paintings from the Netherlandish paintings at a glance. While the subject matter is similar (mostly scenes from the New Testament), and the pigments are basically the same, they used color in completely different ways. I've come to realize that the difference largely comes down to how layering was done.
By layering, I mean variations on glazing. I am using that term broadly to mean any application of two or more layers in which the layers beneath contribute to the final visual effect. Glazing can be done with relatively transparent colors such as red lake, or with opaque colors such as vermillion (if it is applied thinly enough). In both the Netherlandish and Italian traditions, glazing was critical to the final appearance of important parts of almost all paintings, but the way they used glazing was different.
In Netherlandish painting, glazing was used to adjust values with minimal loss of chroma. Typically, an opaque color, such as vermillion, was applied first. The initial layer was typically flat—i.e., with no attempt to model the forms. Then a transparent pigment of similar hue, such as red lake, was applied over the initial flat layer. The transparent color was applied thinly in light areas and thickly in dark areas. Often multiple layers were applied to darks. Because thicker layers of transparent pigments absorb more light than thin layers, a thick layer is darker than a thin layer. This approach to modeling, in which darks are created not with darker colors, but with thicker, light-absorbing layers, creates an optical effect that is completely different than simply mixing a light, a midtone, a dark, and then blending them. Blacks and other dark, dull colors were avoided in Netherlandish glazing. Fully-modeled objects have a jewel-like tonality that jumps off the picture. This glazing technique wasn't used throughout the painting, but was carefully applied in order to control the structure of the composition. It was not used in modeling flesh tones, which were typically done very thinly, in one or two layers.
In Italian painting, by contrast, glazing is used to generate hues through optical mixing of layers. For example, in early Renaissance Italian tempera painting, flesh tones are created by first applying a layer of dull green, then modeling in a dark dull brownish green. On top of that, the flesh color is created by applying an opaque pink (flake white mixed with vermillion) thinly enough that the underpainting shows through. Later in the Renaissance, when Netherlandish oil paintings began to be imported, the Italians tried to copy those effects in oil paint. But while they knew how to make oil paint, they didn't know about Netherlandish layering. They created darks by mixing dark dull colors, including black. Italian oil paintings from that period show none of the chroma intensity in the darks that make Netherlandish paintings so special. It wasn't that they were stupid; it was that they thought about color and layering in a different way, and that approach created a different set of effects. The Italian method was also useful. Botticelli, for example, underpainted foliage with black before glazing over with greens. This makes the foliage fade into the background. He underpainted flesh with yellow ochre, to make flesh tones that had a warm cast. Michelangelo used a traditional (and then somewhat old-fashioned) underpainting with greeen earths for flesh tones. If he wanted two different tones of blue drapery in a painting, he would underpaint one with black, then ultramarine mixed with varying amounts of white and black. The other would be done in the same set of ultramarine gradations over white gesso, creating two completely different ranges of blue with the same surface pigment. Leonardo's sfumato method involved a very dark underpainting in dull earth tones, followed by glazing with light colors mixed with a lot of white. Italian painting is generally brighter and more chromatic than Netherlandish painting, but the darks are more dull. The eye picks up on these differences very easily.
It's useful to understand how both of these kinds of layering effects are accomplished, because if you know how to do both, you have a broad range of useful tricks.