Sono-guided fine needle aspiration (FNA) of the thyroid is widely used, but the aspirated samples are typically not well preserved and low cellularity makes diagnosis difficult in many cases. The object of the current study is to evaluate the adequacy and diagnostic accuracy of the use of $SurePath^{TM}$ liquid-based cytology (SP-LBC) in the sonoguided fine needle aspiration of the thyroid nodule and to compare its use with that of the use of a conventional smear (CS). A total of 172 sono-guided FNAs of thyroid nodules from April to June, 2006 were prepared by the use of the split method with either SP-LBC or CS; the samples were stained with the use of hematoxylin-eosin (H&E) and Papanicolaou (Pap) stains. A cyto-histological correlation was performed in 69 (30 SP and 39 CS) cases that had been histologically confirmed. The rate of producing unsatisfactory slides by the use of the SP-LBC method (9.3%) was less than that of the use of the CS method (20.9%). The diagnostic accuracy of the SP method (93.3%) was better than that of the CS method (85.3%). The sensitivity and specificity of the SP method (94.4% and 92.3%) was better than that of the CS method (83.3% and 70%), respectively (p < 0.05). The CS of sono-guided aspirated specimens had some unavoidable limitations related to inadequate sampling such as a bloody background, low cellularity and an indication that some clinicians smeared many useless slides (averaging four to ten slides), and that most slides showed only blood that included few follicular cells. The SP method resulted in more thinly smeared slides and showed cleaner background and greater cellularity than the use of the CS method. Each follicular cell shows superior nuclear detail, and more distinct cytoplasmic features than with the use of the CS method. SP-LBC appears to be an easy, highly accurate, and reliable cytological method for employ for a diagnostic approach of thyroid disease and thyroid nodules. The SP-LBC method is a suitable alternative to the CS method to overcome diagnostic difficulties.