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Background: To assess skin involvement in a cohort of patients with systemic sclerosis (SSc) by comparing results obtained from modified Rodnan skin score (mRSS), durometry and ultra-high frequency ultrasound (UHFUS). Methods: SSc patients were enrolled along with healthy controls (HC), assessing disease-specific characteristics. Five regions of interest were investigated in the non-dominant upper limb. Each patient underwent a rheumatological evaluation of the mRSS, dermatological measurement with a durometer, and radiological UHFUS assessment with a 70 MHz probe calculating the mean grayscale value (MGV). Results: Forty-seven SSc patients (87.2% female, mean age 56.4 years) and 15 HC comparable for age and sex were enrolled. Durometry showed a positive correlation with mRSS in most regions of interest (p = 0.025, ρ = 0.34 in mean). When performing UHFUS, SSc patients had a significantly thicker epidermal layer (p < 0.001) and lower epidermal MGV (p = 0.01) than HC in almost all the different regions of interest. Lower values of dermal MGV were found at the distal and intermediate phalanx (p < 0.01). No relationships were found between UHFUS results either with mRSS or durometry. Conclusions: UHFUS is an emergent tool for skin assessment in SSc, showing significant alterations concerning skin thickness and echogenicity when compared with HC. The lack of correlations between UHFUS and both mRSS and durometry suggests that these are not equivalent techniques but may represent complementary methods for a full non-invasive skin evaluation in SSc.