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We report an extensive characterization of the Na⁺/monocarboxylate transporter (SMCT), a plasma membrane protein that mediates active transport of monocarboxylates such as propionate and nicotinate, and we show that SMCT may play a role in colorectal cancer diagnosis. SMCT, the product of the SLC5A8 gene, is 70% similar to the Na⁺/I⁻ symporter, the protein that mediates active I⁻ uptake in the basolateral surface of thyrocytes and other cells. SMCT was reported in the apical surface of thyrocytes and formerly proposed also to transport I⁻ and was called the apical I⁻ transporter. However, it is now clear that SMCT does not transport I⁻. Here we demonstrate a high-affinity Na⁺-dependent monocarboxylate transport system in thyroid cells, which is likely to be SMCT. We show that, whereas thyroidal Na⁺/I⁻ symporter expression is thyroid-stimulating hormone (TSH)-dependent and basolateral, SMCT …