Oral squamous cell carcinoma is a potential long-term complication after hematopoietic stem cell transplantation. This may be related to mechanisms including radiation and chemotherapy regimens, chronic graft-versus-host disease, inflammation, and prolonged immunosuppression. The current case describes the development of multiple oral white thick keratotic lesions in the floor of the mouth and the tongue 6 years after hematopoietic stem cell transplantation complicated with chronic graft-versus-host disease. A biopsy performed with histopathological analysis revealed a well-differentiated squamous cell carcinoma. The patient was treated by subtotal glossectomy, bilateral neck dissection, and flap reconstruction. This report highlights the significance of the routine oral examination of long-term surveillance post hematopoietic stem cell transplantation to ensure early detection of these tumors at potentially treatable stage.