It has been suggested that gains of chromosomes 7 and 17 and loss of Y occur in renal papillary adenoma and that progression to papillary renal cell carcinoma is marked by gains of additional chromosomes, most frequently 12, 16, and 20. Previous studies have included very few lesions of <5 mm in diameter, a requirement of the present definition of papillary adenoma. Ten papillary adenomas (ranging from 1 to 5 mm in diameter) from autopsy material and 10 surgically resected papillary renal cell carcinomas were studied with fluorescence in situ hybridization in paraffin sections using centromeric probes for chromosomes 7, 12, 16, 17, 20, and Y diluted 1:100 with tDenHyb1 buffer. The signals in 50 to 150 nuclei were counted in each tumor. Controls for all the probes were normal renal tissues from the same patients. Three or more signals per nucleus were frequently observed in papillary adenomas: chromosome 7 (range, 10 to 50%; > or = 30% in 9 of 10), 17 (range, 10 to 47%; > or = 30% in 7), 16 (range, 1 to 63%; > or = 10% in 5), 12 (range, 0 to 32%; > or =10% in 4), and 20 (range, 5 to 49%; > or = 10% in 5). Loss of the Y chromosome was observed in 80 to 90% of nuclei in 9 adenomas from males. Three or more signals were frequent in papillary renal cell carcinomas: chromosome 7 (range, 32 to 63%; > or =30% in 10 of 10), 17 (range, 28 to 61%; > or = 30% in 7), 16 (range, 0 to 45%; > or = 10% in 6), 12 (range, 1 to 37, > or = 10% in 5), 20 (range, 2 to 44%; > or = 10% in 4). No signal for Y was observed in 12 to 88% (> or = 81% in 6) of nuclei in 7 carcinomas from males. Statistical analysis showed no difference between adenomas and carcinomas. Gains of chromosomes 7, 17, 16, 12, and 20 and loss of the Y chromosome occur early in the evolution of papillary renal cell neoplasia in tumors that are only a few millimeters in diameter. Progressive gains of these chromosomes do not appear to correlate with the transition from adenoma to carcinoma.