Aims: To evaluate the pre-surgical diagnostic value of Multiparametric Ultrasound (MPUS) and Fine Needle Aspiration Cytology (FNAC) in differentiating parotid gland tumors, comparing the results with histology. Materials and methods:The study enrolled 84 patients with parotid gland lesions surgically treated in a single tertiary center and evaluated by MPUS. Each patient underwent FNAC. Histological examination was considered the gold standard. Results: Histology identified 62 benign tumors and 22 malignancies. In the differential diagnosis between malignant and benign lesions, B-mode Ultrasound (US), Color-Doppler US, Contrast-Enhanced US (CEUS), Elastography (USE) and FNAC showed the following values of sensitivity: 82%, 81%, 86%, 77%, 73% respectively; specificity: 97%, 61%, 95%, 71%, 97% respectively; PPV: 90%, 43%, 86%, 50%, 89% respectively; NPV: 93%, 90%, 95%, 88%, 91% respectively; and accuracy: 89%, 71%, 90%, 78%, 84% re-spectively. Conclusions: CEUS proved to be a valid and accurate method for identifying malignant tumors of parotid gland; the combination of B-mode US with CEUS showed similar diagnostic accuracy, but better sensitivity than CEUS taken alone. USE did not improve the diagnostic performance of the B-mode US, alone or in association with CEUS; however, it revealed the highest diagnostic accuracy in the differentiation between benign lesions. FNAC demonstrated lower values in comparison with CEUS and with USE. Therefore, according to our study, MPUS could be proposed as a valid alternative to FNAC.