The majority of medicine is practiced somewhere between the poles of clinical certainty and frank uncertainty. The detection and risk stratification of thyroid nodules operates broadly within this spectrum, relying on a small armory of discrete techniques to nudge clinical decisions closer to the former category rather than the latter. Fadda et al. now suggest that a further nudge towards clinical certainty could result from adding the immunostaining for two protein markers-galectin-3 and the monoclonal antibody HBME-1-in fine needle aspirates to this armory.International guidelines recommend that, after thyroid nodules are stratified for malignancy risk by clinical evaluation, high-resolution ultrasonography and high-sensitivity TSH assay, fine needle aspiration biopsy (FNAB) findings should guide clinical management. Whilst preoperative FNAB reduces the number of surgeries for thyroid nodules considerably, a number of patients undergo 'diagnostic surgery', especially when lesions are classified cytologically as 'indeterminate', which encompasses fol-licular neoplasms and the atypia of unknown significance (AUS) category of the Bethesda classification.
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