Prostatic cancer frequently shows striking morphological heterogeneity and multifocal growth. To better understand the relationship between chromosomal changes and pathological characteristics, 31 routinely processed radical prostatectomy specimens were studied for the presence of numerical chromosomal aberrations by in situ hybridization with centromeric nucleic acid probes specific for chromosomes 7, 10, 17, X, and Y. In 24 of the cases preoperative core biopsy specimens were available and were examined with the probe for the X chromosome. In eight of the prostatectomy specimens chromosome numbers consistent with a normal male karyotype were found. Three cases, besides diploid chromosome numbers, showed a focal doubling of hybridization signals, consistent with tetraploidy. The other 20 cases displayed numerical chromosomal aberrations to a various degree. In this group the appearance of numerical chromosomal aberrations often showed considerable local heterogeneity, generally coinciding with morphological dedifferentiation, and was significantly correlated with tumor stage (P = .0004) as well as primary (P = .0068), worst (P = .0002), and combined (P < .0001) Gleason grades, total tumor volume (P = .0448), and the volume of tumor with Gleason grades 4 or 5 (P < .0001). In four of the 24 core biopsy specimens no residual tumor tissue was left for cytogenetic examination. In the remaining 20 biopsy specimens the presence or absence of numerical changes matched the result obtained on the corresponding prostatectomy specimen. We conclude that in prostatic cancer the presence of numerical chromosomal aberrations is associated with advanced disease. Especially in low differentiated tumors local heterogeneity in 2chromosome numbers can be very marked. It is possible to forecast the presence or absence of numerical chromosomal changes on preoperative core b6iopsy specimens. © 1994.