Thirty-one patients with advanced, biopsy-proven squamous cell carcinoma (SCC) of the head and neck were treated with intraarterial chemotherapy (IAC) and subsequent radical surgery. Cisplatin at 25 mg/d (4 hours of infusion) and bleomycin at 15 mg/d (20 hours of infusion) were administered for 10 consecutive days. Radical surgery was performed after clinical evaluation 2 weeks later. Clinical tumor regression (total disappearance or shrinkage of the tumor mass by more than 50%) was recorded in 28 of 31 (90.3%) patients. Tumor regression was then assessed pathologically using a procedure based on examination of large serial histologic sections of the whole surgical specimen. Tumor residue was classified pathologically according to the TNM categories: RO, no residual tumor (five cases [16.1%]); R1, microscopic residual tumor (tumor residue detectable only at the microscopic level; 12 cases [38.7%]); and R2, macroscopic residual tumor (tumor mass detectable also on the fresh or fixed specimen and/or by the naked eye on the stained tissue sections; 14 cases [45.2%]). Moreover, tumor cell and/or stromal changes possibly associated with tumor regression were found in 77.4% of the cases. Metastatic lymph nodes were found in 12 cases (38.7%), and regression changes were observed in most lymph node metastases. Only standardized, prospective pathologic protocols for the analysis of whole specimens by serial sections permit the assessment of existing tumor residue. The TNM classification of pathologic tumor residue and definitions that we used appear feasible and reliable enough in evaluating postchemotherapeutic tumor regression.