Alterations in 5 microsatellite loci were analyzed in tumors from 137 patients with primary non-small cell lung carcinomas that were also genotyped for the Hras1 variable number of tandem repeats (VNTR) locus. Twenty-nine patients (21%) had changes in at least one microsatellite locus. A majority of these cases (24 of 29, 83%) had VNTR alleles classified as rare in the population. The frequency of these rare alleles were significantly higher among lung cancer patients than in healthy controls (P = 0.016 or 1.80; 95% confidence interval = 1.13-2.85). Microsatellite alterations were significantly more frequent among patients with at least one rare Hras1 VNTR allele (24 of 40, 60%) compared to patients with two common alleles (5 of 97, 5%; P < 0.001 or 27.6; 95% confidence interval = 8.18-82.9). Microsatellite alterations were also more frequent among patients below 50 years of age (8 of 21, 38%) than for older patients (21 of 112, 19%).