Most people’s two eyes are close to identical. They share the same genes, the same blood supply and the same developmental history, so they usually settle on the same shade of brown, green or blue. That’s why a person with one brown eye and one blue eye catches our attention. Something that normally happens in perfect symmetry has, for once, happened unevenly.

The condition is called heterochromia, from the Greek for “different colors.” It is generally estimated to affect fewer than 1 in 100 people, though a 2022 study published in Journal of Optometry notes that a precise figure remains surprisingly elusive. It comes in three main forms.

In complete heterochromia, one iris is a different color from the other. In sectoral heterochromia, a wedge or patch of one iris differs from the rest. In central heterochromia, a ring of color around the pupil contrasts with the outer iris. The central form is often subtle enough to go unnoticed.

Eye Color Is Mostly About One Pigment

To understand why eyes mismatch, it helps to know what makes them colored at all. Surprisingly, human irises contain essentially one kind of pigment: melanin, the same pigment that colors skin and hair. It is made by specialized cells called melanocytes.

Brown eyes have a lot of melanin in the front layers of the iris, as a 2009 review published in Pigment Cell & Melanoma Research lays out. Blue eyes have very little, and they contain no blue pigment. Their color comes from the way the iris tissue scatters light, the same basic physics that makes the sky look blue. Green and hazel eyes sit in between , with moderate melanin combined with that scattering effect.

Several genes influence how much melanin the iris makes. Two neighboring genes, OCA2 and HERC2, play an outsized role. According to a 2008 study published in The American Journal of Human Genetics , a small change in HERC2 appears to act like a dimmer switch on OCA2, turning down pigment production in the iris. Still, eye color is polygenic, meaning many genes each contribute a little.

So heterochromia almost always boils down to one question: why did one iris, or part of one, end up with more or less melanin than the other?

From The Embryo To The Eye

The answer usually lies in early development. Melanocytes don’t start out in the eye. They descend from neural crest cells, a population of embryonic cells that form along the developing brain and spinal cord and then migrate throughout the body. They go on to form parts of the face, the nervous system and the pigment cells of the skin, hair and eyes.

Think of it like settlers spreading across a new territory. Most regions get populated evenly, but a random stall or detour can leave one valley thinly settled. If fewer pigment cells reach one iris, or they arrive but produce less melanin, that eye ends up lighter.

This is why many cases of congenital heterochromia, the kind present from birth or infancy, are simply harmless quirks of development. Genetic mosaicism, in which a person carries slightly different genetic instructions in different groups of cells, can produce the same patchy effect. Most people born with mismatched eyes have healthy, normally functioning vision.

In a minority of cases, heterochromia is one sign of a broader condition. Waardenburg syndrome, a genetic condition that affects neural crest cells, can cause vivid blue or mismatched eyes along with patches of white hair and, in some people, hearing loss.

Congenital Horner’s syndrome, which involves the nerves serving one side of the face, can also leave one iris lighter, since those nerves appear to help pigment develop in the eye during early life.

When Eyes Change Color Later In Life

Heterochromia can also appear in adulthood, and here the picture is different. Eye injuries, bleeding inside the eye, certain types of chronic inflammation and, rarely, tumors can alter the color of one iris. Some glaucoma eye drops are known to darken the iris gradually over time.

For that reason, eye doctors generally advise that a noticeable color change in one eye in an adult should be checked. The change itself is rarely dangerous, but it can be a useful signal of something going on beneath the surface.

Why Your Cat’s Eyes Are More Likely To Have It

Heterochromia is rare in people but relatively common in some animals. Odd-eyed white cats, huskies, Australian shepherds and certain horse breeds show it often. The reason is that many of these animals carry genes for white coats, white spotting or other patterns that dilute pigment, which work by limiting where pigment cells settle or how much pigment they make during development. In cats, a 2014 study published in G3: Genes, Genomes, Genetics traced both white coats and white spotting to changes in a single gene called KIT. When that effect extends to one eye, it stays blue.

The same developmental link explains a well-known pattern in white cats: deafness is more common among blue-eyed individuals, sometimes on the same side as the blue eye. The inner ear also depends on cells derived from the neural crest, so the two traits can travel together.

One of the most famous “heterochromia” example is actually not heterochromia at all. The musician David Bowie is widely described as having two different-colored eyes, but his irises were both blue. After an injury in his youth, one of his pupils stayed permanently dilated, a condition called anisocoria, which made that eye look darker.

That mix-up reflects something true about the real trait. Eye color can look like a fixed, simple feature, but it is the end result of a long developmental process. Heterochromia is a rare, visible reminder that our bodies are built by cells that must travel, settle and switch on at just the right time, and that sometimes, harmlessly, they do so unevenly.

Surprised that blue eyes contain no blue pigment at all? Find out how much you really know about the inner workings of your own body with this science-backed test: Human Anatomy IQ Test