Genetic predisposition to lung cancer was determined by observing nonrandom chromosomal alterations in peripheral blood lymphocytes (PBLs) of lung cancer patients. The histological distribution of the cases showed that chromosomes 7 and 9 were frequently altered in squamous cell lung carcinoma (SCLC) patients. We analyzed PBLs of 26 SCLC patients and 5 controls using fluorescent in situ hybridization (FISH) with whole chromosome painting probes of chromosomes 7 and 9 to further investigate the frequency of rearrangements in these chromosomes. Our results suggested that seeking nonrandom aberrations in larger numbers of cells using FISH strengthened our previous observation of mosaicism and involvement of specific chromosomes in lung cancer patients. On combining our previous data, aberrations in chromosome 7 (16 of 26 patients), chromosome 9 (14 of 26), and the present study, we could actually pinpoint more individuals with abnormalities of chromosome 7 (23 of 26) and chromosome 9 (21 of 26). Thus, analyzing more cells in PBLs and adding FISH analysis serve as useful adjuncts to our studies of nonrandom chromosomal aberrations and genetic mosaicicm.