Interphase fluorescence in situ hybridization (FISH) is particularly useful for detecting chromosome changes in tumors exhibiting a low mitotic index, as is the case in many human non-small cell lung carcinomas (NSCLCs). A panel of centromeric DNA probes specific for the autosomes 6, 7, 8, 9, 12, 17, and 18 was used to analyze 17 primary NSCLCs. Evidence for aneuploidy was obtained in all specimens. Gain of part or all of chromosome 7 was especially prominent, occurring in a large population of cells in each of 14 tumors (82%). Extra centromeric copies of chromosomes 6, 12, and 17 were also common, being observed in 9 to 11 cases each. Gain of chromosome 9 was infrequent (three tumors). In two cases, most of the nuclei had only a single chromosome 9 fluorescent signal. Karyotypic findings were available for six cases and were generally consistent with the FISH data. Both methods revealed considerable heterogeneity within individual tumors. NSCLC specimens from 26 males were assayed with a Y-specific centromeric sequence; loss of the Y was observed in 13 cases (50%). These investigations demonstrate the feasibility of interphase FISH for the successful analysis of numerical chromosome changes in NSCLCs.