OBJECTIVE Prospective evaluation of the diagnostic outcome of plain and signal-enhanced color Doppler sonography for the differentiation between benign and malignant cutis-involving lesions. METHODS 39 patients with 40 suspected malignant skin lesions received an preoperative ultrasound examination before and after application of 4 g Levovist i.v. Spectral Doppler, conventional color and power Doppler were performed. The images were analyzed semiquantitatively using a specially developed software. The diagnoses were confirmed by histological analysis (37 cases) or by follow up controls (3 cases). RESULTS Whereas the B-mode criteria such as echogenoity, borderline and homogenecity, and the spectral Doppler analysis were not useful for differentiation between malignant and benign lesions, the analysis of the intratumorously visible number of vessels and of the ratio of the vascularized area using a special software, especially after injection of the signal enhancing agent, provided valuable information. In 10 of 18 benign but only in 1 of 22 malignant lesions, no intratumorous vessels were visible after application of Levovist (plain: 10/18 benign and 6/22 malignant lesions). The number of visible vessels increased strongly after signal enhancement. Using a "ratio of the vascularized area (percentage vessel area) > 5%" as a criterion of malignancy, 2 false positive and 2 false negative results were observed after application of Levovist (without/with Levovist sensitivity 73%/91%, specificity 89%/89%). CONCLUSIONS The signal-enhanced color Doppler sonography provides useful additional information for the differentiation between benign and malignant cutis-involving lesions, especially the semiquantitative vascularization analysis. The latter is superior to B-mode ultrasound and to spectral Doppler analysis. The signal enhancer increases the sensitivity, whereas the specificity remains unchanged.