Loss of heterozygosity (LOH) correlates with inactivate tumor suppressor gene. The aim of this study was to see if LOH on chromosomes 2q, 3p and 21q correlated with a poor prognostic factor in oral squamous cell carcinoma (SCC). We analyzed chromosomes 2q, 3p and 21q for LOH in 40 primary oral SCCs using 30 markers and constructed a deletion map for these chromosome arms. Significant LOH (>20%) occurred at alleles in chromosome bands 2q14-21 (21.7%), 2q32-35 (31.6%), 2q35 (21.1%), 2q36 (36.7%), 3p25 (32.4%), 3p21.3 (23.8%), 21q11.1 (52.4%), 21q21 (21.6%) and 21q22.1 (22.2%). A significant correlation was observed between the number of regions showing LOH at 2q and TNM clinical stage (P = 0.0063), consistent with the progressive accumulation of genetic errors during the development oral SCC The number at more than two LOH loci was significant with a poor prognosis at 2q (P = 0.0208). These findings demonstrate that oral SCC exhibits genetic alterations at multiple loci and that allelic loss at more than two locations is indicative of a poor prognosis. This is the first study to demonstrate the prognostic significance of LOH at 2q, 3p and 21q for oral cancer and may help to identify patient who should receive more aggressive treatment. (C) 2003 Elsevier Ltd. All rights reserved.