Abstract This is a report of two patients (brothers) with unusual generalized skin disorder, a recessive dystrophic epidermolysis bullosa (RDEB) that appeared at childhood, who developed a progressive squamous cell carcinoma (SCC) in their right hands. Later both patients underwent wide local tumor excision, and during the follow-up after surgery, axillary lymph node metastasis observed in the first case, and local recurrence in the second. Therefore early recognition of EBD is important to assist in the diagnosis and treatment of malignant lesions at an early stage in these patients to prevent the subsequent complications.