Huriez syndrome is a rare genodermatosis, which is characterized by palmoplantar keratoderma, sclerodactyly, nail abnormalities, and an increasing risk of squamous cell carcinoma. The exact causative gene and pathogenesis of Huriez syndrome have not been identified. We herein introduce a case of 62-year-old woman with Huriez syndrome who developed squamous cell carcinoma in her 60s. This case underscores the importance of early detection of this disease due to its aggressive carcinogenic nature with high metastatic potential. Regular and detailed clinical follow-ups are needed to prevent morbidity and provide appropriate treatment for skin cancers in affected patients.