Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China, especially in the Guangdong area. To demonstrate a comprehensive profile of loss of heterozygosity (LOH) in NPC, we applied a large panel of 382 microsatellite polymorphism markers covering all the 22 autosomes in 98 cases of sporadic primary NPC. Of the 335 informative markers, 83 loci showed high level of LOH (presence in equal to or more than 30% cases) and most of the high frequent loci were clustered to chromosome 1p36 and 1p34, 3p14-p21, 3p24-p26, 3q25-q26 and 3q27, 4q31 and 4q35, 5q15-21 and 5q32-q33, 8p22-p23, 9p21-p23 and 9q33-q34, 11p12-p14, 13q14-q13 and 13q31-q32, 14q13-q11, 14q24-q23 and 14q32. High frequency of LOH was found in chromosomes 3, 5, 9 and 11 (>/=50%), while medium frequency of LOH was found in chromosomes 1, 4, 6, 14, 17 and 19 (40-49%). Several new regions showing high frequency of LOH were found in chromosome 1p36, 3q25-q26, 3q27, 5q15-q21, 8p22-p23 and 11p12-14. The relationship between LOH and TNM stage of NPC was evaluated. Regions 6p23 (D6S289), 8p23.1 (D8S549) and 9q34.2 (D9S1826) showed higher frequency of LOH in later stages (III and IV) than in earlier stages (I and II) (P<0.05). Thus, our study provides a global view on allelic loss in the development of NPC and should shed light on the way for localization of putative tumor suppressor genes associated with the pathogenesis of NPC.