Metastases to skeletal muscle and paraneoplastic syndromes involving β-human chorionic gonadotropin (HCG) production are an extremely rare manifestation of head and neck squamous cell carcinoma. We report a patient with a β-HCG-secreting squamous cell carcinoma of the tongue with diffuse metastases involving skeletal muscle. A 47 year old female, who was being treated heavily with palliative chemotherapy for metastatic tongue cancer, was admitted with a palpable thigh mass and pain. A magnetic resonance image showed an intramuscular metastasis in the thigh. Ultrasound-guided biopsy of the thigh mass confirmed metastatic squamous cell carcinoma. She was scheduled for enrollment into a clinical trial; however, a positive serum β-HCG test was noticed. There was no evidence of pregnancy or a trophoblastic or non-trophoblastic tumor secreting β-HCG. Finally, she was revealed to have a paraneoplastic syndrome with diffuse metastases and was ultimately referred for palliative care. We review the literature of previously reported cases of an increase of β-HCG in patients with head and neck cancer. (Korean J Med 2015;89:719-722)