The vast majority of lesions in grey horses are benign tumors but the course of the disease varies with the individual. Some horses develop a few bumps then stop. While others rapidly develop dozens of nodules in a short time. The rate of growth is very variable from no growth for years to doubling its size every few months. As they grow and left untreated they may coalesce into larger clusters. It is important to note that grey horse melanomas do not spread through metastasis, where cells from one tumor spreads, either through the blood stream or local invasion of surrounding skin, to other areas. Instead the melanocytes, the cells that produce the pigment in the skin, have become neoplastic individually. There is strong evidence that this is do to a genetic defect common in grey horses.

In some individuals the nodules will begin to grow in clusters and rapidly. Untreated some of these tumors can get several inches across. Unlike melanomas in humans the disease is usually not malignant in grey horses. Some large tumors will occasionally break open and discharge a black exudate and probably represents an area of necrosis within the tumor or possibly some exudate formed by the cancer cells themselves. Some dry up and stop only to repeat it at a later date or some just continually drain the black liquid.

One complication of rapidly growing clusters is ulcerations forming where the melanomas rub against each other. Usually secondary infections with an odorous purulent discharge can make for a messy unpleasant, but not life threatening condition. It is very hard to treat these lesions as so much of the skin in these areas have been destroyed.

Non-grey horses with melanomas have a high rate of malignancy with early metastasis to the internal organs.