The most common cause of apparent ineffectiveness or resistance to treatment with oral levothyroxine (LT(4)) is the result of noncompliance, known as pseudomalabsorption. However, an abnormality in the bioavailability of LT(4) should also be considered in patients requiring large doses of LT(4) to achieve euthyroidism. The incidence of lactose intolerance in Caucasian adult patients is 7%-20%, but the association with resistance to treatment with oral LT(4) is unusual. We report a 55-year-old woman in whom treatment LT(4) for hypothyroidism was found related to a previously undiagnosed oligo-symptomatic lactose intolerance, an unusual association. Although rare, intolerance to lactose should be considered in the differential diagnosis of gastrointestinal diseases that can cause malabsorption of LT(4). The possibility of correcting this disorder with simple dietary measures justifies its consideration.