OBJECTIVE: To describe the natural history and evaluate the prognosis of basaloid squamous cell carcinoma (BSCC) of the upper aero-digestive tract as compared to the usual squamous cell carcinoma (SCC). MATERIALS AND METHODS: Sixty-two patients with BSCC and 62 patients with SCC were matched with regards to TNM classification, localisation and therapeutic modalities. Histological criteria, follow-up and 5-year survival were compared among the two groups. RESULTS: Survival rates were significantly higher in patients with SCC as compared to patients with BSCC. The rate of distant metastasis was six times higher in cases of BSCC, which was the major cause of mortality. CONCLUSION: This study reveals that BSCC has distinct histo-pathologic features and an aggressive clinical course, justifying its consideration as a separate entity with poor prognosis. The authors propose to systematically perform a chest CT-scan and FDG-PET to rule out early distant metastasis and to include adjuvant chemotherapy in treatment protocols.