AIM: Free and pedicled flap are methods of choice for reconstruction of post-surgical defects consequent to oral squamous cell carcinomas (SCCs), and missing intraoral mucosa is commonly reconstructed by the cutaneous component of the flap to guarantee an epithelial lining. Even if rare, cases of second tumors arising in the skin flap have been described. We present our experience reporting a clinical case. CASE REPORT: A squamous cell carcinoma arose on a forearm free flap 21 years after hemiglossectomy in a 72 years old woman. No smoking or alcohol habits were referred, and it was decided to perform surgical resection of the flap. RESULTS: Resection in free margins of a moderate differentiated (G2) SCC staged as pT2 was achieved and reconstruction with anterolateral thigh free flap was performed. DISCUSSION: Even if rare, secondary tumors arising in the skin flap in case of oral cavity defects reconstruction are described. It is important to recognize them early in order to perform surgical resection. CONCLUSION: We think that it is fundamental to perform a prolonged follow-up of skin flap if a white patch or erythema raising clinical suspicion are present. Incisional biopsy has to be performed in order to identify those lesions potentially inclined to a malignant transformation, such as p53 expression and Ki67 index.