The aims of our study were to evaluate with ultra-high-frequency ultrasound (UHFUS) the ultrasound features of congenital melanocytic nevi (CMNs) and malignant melanomas (MMs) arising in CMNs and the correlation between ultrasonographic thickness and histological thickness in MMs. We evaluated 10 patients with small-medium CMNs and 10 patients with MMs arising in small-medium CMNs. We collected patient's data, clinical and dermoscopic features. The UHFUS was performed using a 70 MHz frequency probe to study the ecostructure, shape and vascularization. Breslow thickness was compared with ultrasonographic thickness. In the MMs group the following dermoscopic features were described: hyperpigmentation (n = 9), regression area (n = 6), whitish-blue veil (n = 5), thickened network (n = 5), irregular globules (n = 3), inverse network (n = 2) and striae (n = 1). Hyperpigmentation (n = n = 9), thickened network (n = 7), irregular globules (n = 5), regression area (n = 5), striae (n = 1) and whitish-blue veil (n = 1) were found in the CMNs group. The multicomponent pattern was present in both MMs (n = 4) and in CMNs (n = 5). Moreover, the parameters indicative of suspected malignancy were variously combined in the two groups, without showing significant differences in the statistical analysis; with the exception of the blue veil that correlated with the diagnosis of MM. Ultrasonoghaphic vascularization was an ever-present parameter in MMs (100%), with high intensity of intratumoral signal, as opposed to CMNs. We also found a statistically significant correlation between ultrasound thickness and Breslow thickness. In the future, this technique could implement the diagnostic preoperative phase of MMs arising in CMNs in combination with standard clinical-dermatoscopic evaluation.