To verify whether the use of second generation ultrasonographic contrast agents leads to an improvement in the differential diagnosis of thyroid nodules, twenty patients, eligible for uninodular goiter surgery were studied. All patients previously underwent complete hormonal profile, bidimensional thyroid ultrasonographic, Colour Doppler evaluation and 99 mTc scintiscan. All nodules were as well evaluated before and after sulphur-hexafluoride administration. Wash-in time, contrast agent intra-nodular flow and wash-out time were evaluated. These data were compared with the cytology and histology findings. On the basis of the histological examination we divided our study population in 2 groups: in the group of neoplastic lesions (4 follicular adenomas and 6 carcinomas) an early wash-in was observed, with an homogeneous peripheral pattern enhancement, a rapid centripetal progression and an extended persistence of the contrast agent inside the nodule. In 6 out of 10 cases of thyroid neoplasia a fast wash-out was observed. In the group of benign lesions, in the patients affected by nodular goiter, an intra-nodular perfusion as opposite to the healthy surrounding parenchyma was observed. Even though ultrasound contrast agent technique has a limited invasivity and is more expensive than Fine Niddle Aspiration (FNA), the preliminary data of this pilot study suggest that this method might prove useful, to differentiate benign from malignant thyroid nodules.