Allelic loss is a common occurrence in head and neck tumors and has been shown to be an independent predictor of prognosis; however, the relationship between allelic loss and tumor pathology is not well-known. We studied 139 patients who were newly diagnosed with squamous cell cancer of the head and neck to determine whether tumor pathology was correlated with allelic loss at one or more of eight different regions on chromosomes 3p, 5q, 8p, 9p, 10p, 18q, and 21q. At each chromosomal region, loss of heterozygosity at any one of three or four highly polymorphic microsatellite markers that spanned the region in question was considered evidence for allelic loss. A pathologist scored all tumors for seven tumor pathology and host interface parameters. Mean allelic loss across all eight regions was associated with mitotic index (P =.034) and inflammatory response (P =.005). For allelic loss at specific chromosomal regions, the most statistically significant trends were between overall tumor grade and 3p14.2-p13 (P =.014), mitotic index and 3p24.3-p14.3 (P =.026), 9p24.2-p21 (P =.004) and 18q12.3-q23 (P =.009), inflammatory response and 3p14.2-p13 (P =.008) and 9p24.2-p21 (P =.001), desmoplastic response and 9p24.2-p21 (P =.009), and pattern of invasion and 21q21-q22.2 (P =.015). Our results suggest that genes involved in tumor suppression and oncogenesis can potentially be classified based on specific pathologic events in head and neck squamous cell carcinogenesis that they modify.