Objective: High-resolution computed tomography (HRCT) may lack sensitivity for the early detection of interstitial lung disease associated with systemic sclerosis (SSc-ILD). Lung ultrasound is an emerging technique for the diagnosis of SSc-ILD. This cross-sectional study aimed to describe the prevalence of ultrasound interstitial syndrome in SSc patients with normal HRCT and pulmonary function tests (PFT). Methods: Thirty SSc patients with normal HRCT, FVC > 80% predicted and DLCO > 70% predicted were included. Echocardiography and PFT including impulse oscillometry and cardiopulmonary exercise testing were performed. Lung ultrasound was analyzed by two blinded operators. Patients were classified into two groups, according to the presence or absence of ultrasound interstitial syndrome, defined as the sum of B-lines in all thoracic areas ≥10 and/or pleural line thickness >3 mm on at least one thoracic area and/or a pleural line irregularity score >16%. Results: Ultrasound interstitial syndrome was present in 12 patients (40%). Inter-reader agreement for the diagnosis of ultrasound interstitial syndrome defined by the Kappa coefficient was 0.93 (95%CI 0.79-1.00). Patients with ultrasound interstitial syndrome were younger (37 years vs. 53 years, p = 0.009), more often had pitting scars (n = 7/12 vs. 3/18, p = 0.045) and had lower FVC (102 vs. 110% pred, p = 0.009), TLC (114 vs. 122% pred, p = 0.042) and low-frequency respiratory system reactance (Xrs5 Z-score 0.16 vs. 1.02, p = 0.018), while pulmonary gas exchange was similar. Conclusions: Ultrasound interstitial syndrome was detected in 12/30 SSc patients with normal HRCT and PFT. Patients with ultrasound interstitial syndrome had differences in lung function consistent with reduced respiratory compliance, suggesting minimal and/or early suspected SSc-ILD.