Natural pearls are nearly 100% calcium carbonate and conchiolin. It is thought that natural pearls form under a set of accidental conditions when a microscopic intruder or parasite enters a bivalve mollusk, and settles inside the shell. The mollusk, being irritated by the intruder, forms a pearl sac of external mantle tissue cells and secretes the calcium carbonate and conchiolin to cover the irritant. This secretion process is repeated many times, thus producing a pearl. Natural pearls come in many shapes, with perfectly round ones being comparatively rare.

Typically the build up of a natural pearl consists of a brown central zone formed by columnar calcium carbonate (usually calcite, sometimes columnar aragonite) and a yellowish to white outer zone consisting of nacre (tabular aragonite). In a pearl cross section such as in Fig. 6 these two different materials can be seen. The presence of columnar calcium carbonate rich in organic material indicates juvenile mantel tissue that formed during the early stage of pearl development.

We know, e.g. from human medicine, that displaced cells with a well-defined task, continue to perform their function. The term "cyst" is applied to such situations. The displacement may occur with an injury. The fragile rim of the shell is exposed and is prone to damage and injury. Crabs, other predators and parasites such as worm larvae may produce traumatic attacks and cause injuries in which some external mantle tissue cells are disconnected from their layer. Embedded in the conjunctive tissue of the mantel, these cells may survive and form a small pocket in which they continue to secrete their natural product: calcium carbonate. The pocket is called a pearl sack, and grows with time by cell division; in this way the pearl grows also. The juvenile mantle tissue cells, according to their stage of growth, produce columnar calcium carbonate, which is secreted from the inner surface of the pearl sack. With ongoing time the external mantle cells of the pearl sack proceed to the formation of tabular aragonite. When the transition to nacre secretion occurs, the brown pebble becomes covered with a nacreous coating. As this process progresses, the shell itself grows, and the pearl sack seems to travel into the shell. However, it actually stays in its original relative position within the mantle tissue. After a couple of years, a pearl will have formed and the shell might be found by a lucky pearl fisher.