We examined loss of heterozygosity (LOH) on all autosomal chromosomes in 53 non-small cell lung carcinomas. Frequent LOH was observed on the long arms of chromosomes 1 (37%), 2 (31%), 5 (30%), 8 (31%), and 13 (32%), and the short arms of chromosomes 3 (54%) and 17 (62%). LOH on chromosomes 3p and 17p was observed in all informative cases of squamous cell carcinoma, but was significantly less frequent in adenocarcinomas (P = 0.003 and 0.001, respectively). Similarly, LOH on chromosome 13q was observed frequently in squamous cell carcinomas (5 of 9 informative cases, or 56%), but in only 5 of 26, or 19%, of adenocarcinomas. In contrast, LOH on chromosome 2q was observed only in adenocarcinomas. In addition, this chromosomal arm was lost more frequently in poorly differentiated, compared to well differentiated adenocarcinomas. Furthermore, a correlation between fractional allelic loss and pathohistological grade was identified. These results implicate the presence of several tumor suppressor genes associated with development and/or progression of non-small cell lung carcinomas.