We designed an open, non-randomized clinical study to assess as the first endpoint the feasibility of sparing surgery and of preserving organ/function by using neo-adjuvant chemotherapy (NAG) in oral cavity and oropharynx cancer patients, and, as the second endpoint, the clinical response to this treatment approach and its duration. Moreover, an attempt was made to scale the extent of surgery by means of an Arbitrary Scale assigning different percentages to the different extents of surgical resection. Twenty-five patients with primary oral cavity and oropharynx cancer (stage III-TV) were enrolled in the study and were assigned to either the classical Al-Sarrafs regimen (1) (n=15) or to a regimen (2) consisting of cisplatin 80 mg/m(2) i.v. on day 1, 5-FU 600 mg/m(2) on days 2-5 and vinorelbine 20 mg/m(2) on days 2 and 8 (n=10). The 25 patients were all evaluable for response to NAC and 20 of them were evaluable for organ preservation. The overall response (OR) rate was 86.6% (13/15 patients) for regimen 1 (cisplatin + 5-FU) and 80% (8/10 patients) for regimen 2 (cisplatin + 5-FU + vinorelbine). The median follow-up duration was 20.6 months. 5/20 (25%) patients completely avoided surgery, 5/20 (25%) patients had a reduced extent of surgical resection, while: 10/20 (50%) patients received the previously planned surgical resection. Altogether, 10/20 (50%) patients treated with NAC either avoided or achieved a reduction in the previously planned surgical resection. Moreover, organ function was evaluated to support the assessment of treatment outcome in our patients. For this purpose we selected the Performance Status Scale for Head and Neck Cancer Patients: as expected, no significant impairment was detected in the area of comprehensibility of speech, but we were rather surprised that no significant impairment was found in the two areas of eating in public and normalcy of diet. NAG-associated toxicity was moderate and similar in the two chemotherapy regimens. The most relevant contributions offered by our study are represented by i) a Scale aimed at measuring as precisely as possible the reduction of surgical resection made possible by NAC compared to surgery planned before NAC and ii) an attempt to support the results with an assessment of treatment outcome.