Biological control over coral skeletal composition is poorly understood but critically important to paleoenvironmental reconstructions. We present microanalytical measurements of trace-element abundances as well as oxygen and carbon isotopic compositions of individual skeletal components in the zooxanthellate coral Colpophyllia sp. Our data show that centers of calcification (COC) have higher trace element concentrations and distinctly lighter isotopic compositions than the fibrous components of the skeleton. These observations necessitate that COC and the fibrous skeleton are precipitated by different mechanisms, which are controlled by specialized domains of the calicoblastic cell-layer. Biological processes control the composition of the skeleton even at the ultrastructure level.