Iron transport in plasma is carried out by transferrin, which donates iron to cells through interaction with a specific membrane receptor. In this review, we summarize the current knowledge on the structure, intracellular cycle, distribution, and regulation of the tissue transferrin receptor. A soluble form of the transferrin receptor has been identified in animal and human serum. We review the molecular form and origin of the soluble receptor, its dosage in normal serum and its relationship with erythropoiesis, iron status, and cancer. Lastly, we discuss the clinical usefulness of the soluble transferrin receptor for the quantitative determination of marrow erythropoietic activity.