From 1980 to 1996, 1,907 consecutive euthyroid subjects with palpable thyroid nodules were examined by fine needle aspiration (FNA) cytology plus large needle aspiration biopsy (LNAB) histology. There were 1,630 (85%) women and 277 (14.5%) men aged from 17 to 80 years. A single nodule was palpated in 1,419 subjects (74.4%) while 488 (25.6%) showed multiple nodules. The nodule size ranged between 1 and 7.5 cm. The number of inadequate specimens at the first examination, FNA cytology of LNAB histology, were 261 (13%) or 398 (20.8%), respectively. LNAB performed on the 261 nodules with nondiagnostic cytology showed findings which were adequate for diagnosis in 130 (49.8%) and inadequate in 131 (50.2%). Among the 261 patients with inadequate initial cytological findings 61 were subjected to repeated FNA and 36 repeated LNAB. More than 60% of the nodules on which FNA was repeated achieved a cytological diagnosis; more than 80% of the nodules reinvestigated by LNAB were finally diagnosed by histology. The mean nodule size was larger in the group with inadequate result than in that with adequate FNA or LNAB result. Among the 261 patients with inadequate cytological finding at the first FNA 28 were operated on; 20 were in the group with adequate LNAB histological findings and eight in the group with an inadequate LNAB. Two papillary cancers, one per group, were found at postoperative histology. However, one was diagnosed by LNAB and one at the second FNA. The remaining 26 nodules were all found to be benign postoperatively. This study shows that the addition of LNAB to FNA leads to a histological diagnosis in 50% of the palpable thyroid nodules with inadequate cytology at the first FNA and that LNAB can be used even for those nodules which remain uncharacterized after repeat FNA.