A foreign substance irritates a specific species of oyster, mussel, or clam, causing it to generate a natural pearl (often known as an Oriental pearl). The mollusk squirts layer after layer of liquid nacre covering the irritant as a defensive mechanism, thus resulting in the formation of a spherical pearl.

A cultivated pearl goes through the same procedure. The distinction is that the irritant is a surgically implanted bead or piece of shell known as Mother of Pearl. These shells are frequently ground oyster shells, which are valuable in their own right as irritant-catalysts for quality pearls. As a result, the resulting core is much larger than that of a natural pearl. However, as long as there are enough layers of nacre (the secreted fluid covering the irritant) to produce a beautiful, gem-quality pearl, the size of the nucleus is unimportant in terms of beauty or durability.