The structure and composition of mantle tissue from red abalone Haliotis rufescens were studied in relation to pearl farming. Histological (hematoxylin-eosin) and histochemical (PAS Alcian Blue, Sudan Black, Dahl's) tools were used to determine variations in the glycogen index, lipid index, and calcium coverage index of mantle tissue as a function of seasonality (cold and warm period) and body region (dorsal, central, ventral). Anatomically, only two well-developed and functional mantle folds (inner and outer) were observed across the marginal zone, together with a poorly developed, and presumably, rudimentary fold with the same cellular morphology as the inner fold. The inner mantle epithelium stored significantly higher concentrations of glycogen and mucins, triglycerides, and calcium than the outer epithelium. This pattern occurred significantly more during the cold season than during the warm season. Mucins from mantle tissue not only regulate crystal nucleation and orientation during biomineralization, but also give the inner nacreous layer its luster and color. High concentrations of lipids in mantle tissue could help compensate for the energy loss caused by the wound-healing processes associated with mantle tissue removal and seeding, which are stressful and energetically costly. The absorption of calcium ions from the environment to integrate a microlaminate of calcareous compounds gives the shell its structural properties of hardness and strength. An approach with molecular-ultrastructural tools is recommended to broaden the understanding of mantle tissue regionalization and its relationship to pearl sac formation, which may help increase pearl yield and quality in H. rufescens.