The incidence of oral squamous cell carcinoma (OSCC) in young and healthy patients has been described and represents only 2% of cancers during pregnancy, usually associated with worse outcome. A nonsmoking 31-year-old woman presented a painful nodular lesion at the hard palate, which overgrew during pregnancy and showed unexpected regression following childbirth. After 1 year the lesion presented as an indurated erythematous plaque with elevated borders at the hard palate expanding to the soft palate. An incisional biopsy specimen showed exuberant hyperplastic epithelium with keratin pearl formation, compatible with well-differentiated OSCC and positivity for p16. She underwent partial maxillectomy with a microvascular free flap reconstruction. Bone and lymph nodes were tumor free, and minor salivary glands were infiltrated. No adjuvant treatment was needed. We report a rare regression phenomenon of OSCC and pose a question whether pregnancy may have contributed to tumor regression, which could guide future therapeutic targets against cancer.