OBJECTIVE Pain is one of the few drawbacks of fine-needle aspiration biopsy (FNAB) in patients with nodular thyroid disease (NTD). Lidocaine/prilocaine cream, an eutectic mixture of local anaesthetics (EMLA), is a frequently used topical anaesthetic. Despite its well-documented efficacy for the relief of pain associated with other cutaneous procedures that involve needle insertion, the analgesic role of EMLA has not been previously reported in patients with NTD who are undergoing FNAB. The aim of this study was to determine the analgesic efficacy of EMLA for FNAB-associated pain in patients with NTD. METHODS Double-blind, placebo-controlled clinical trial. METHODS The study was conducted at a thyroid outpatient clinic. We studied 99 patients with NTD. METHODS Patients with NTD were allocated to receive either 2.5 g of EMLA (n = 50) or placebo (n = 49) 60 min before ultrasonographically guided FNAB. A series of four biopsies of each nodule was performed. Patients rated pain associated with the procedure according to a 100-mm visual analogue scale (VAS), an 11-point numeric rating scale (NRS), and 4-category verbal rating scale (VRS). RESULTS When the EMLA group was compared with the placebo group, there were no significant differences with respect to age, sex, thyroid volume, nodule size or nodule site. Significant differences were noted in the pain ratings of the two groups according to all three pain scales. When the effectiveness of EMLA was compared with that of placebo, the mean VAS score was 25.0 +/- 22.3 mm vs. 40.0 +/- 30.5 mm (P = 0.006) and the mean NRS score was 2.9 +/- 2.3 points vs. 4.0 +/- 2.6 points (P = 0.02). The absolute numbers according to VRS score in each group was also significantly different (P = 0.01). Although our sample size was small, the data suggest that FNAB-associated pain was sex-related and that women were significantly more sensitive than were men (P = 0.003 for VAS score and P = 0.001 for NRS score). No adverse effects from the use of EMLA were reported. CONCLUSIONS To our knowledge, this is the first study demonstrating that a topical anaesthetic, EMLA, provides an effective and noninvasive analgesia during the FNAB of NTD.