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Background  The similar visual appearance of high‐risk basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) may cause confusion for diagnosis. High‐frequency ultrasound (HFUS) may provide additional intralesional information and thus help to distinguish them.    Method  In this retrospective study, we analyzed the clinical characteristics, HFUS grayscale, and color Doppler flow imaging (CDFI) features of pathologically confirmed high‐risk BCC and cSCC lesions ( n  = 65 vs  n  = 68). Subsequently, discrimination models based on the significant HFUS features were established.    Results  Between high‐risk BCC and cSCC lesions, the HFUS grayscale features of the lesion size (10.0 mm vs 17.4 mm), thickness (3.1 mm vs 5.9 mm), internal hyperechoic spots (80.0% vs 23.5%), and posterior acoustic shadowing (16.9% vs 66.2%) were statistically different (all  p  < 0.001). As for the CDFI features, high‐risk BCC lesions mainly appeared as pattern II (47.7%), while cSCC lesions mainly appeared as pattern III (66.2%). Based on the above five features, an optimal discrimination model was established with a sensitivity of 91.2%, a specificity of 87.7%, and an accuracy of 89.5%.    Conclusion  HFUS features, including size, thickness, internal hyperechoic spots, posterior acoustic shadowing, and Doppler vascularity pattern, are useful for differential diagnosis between high‐risk BCC and cSCC.

High‐frequency ultrasound for differentiation between high‐risk basal cell carcinoma and cutaneous squamous cell carcinoma