Very little data have been published on cytogenetic abnormalities in Hodgkin's disease (HD) and their correlation with clinicopathologic features are scanty. We have performed chromosomal analysis of lymph nodes from 60 previously untreated HD patients and obtained analyzable metaphases in 49 patients (82%). Chromosomal abnormalities were found in 33 patients (55%) but only 31 karyotypes could be, at least partially, described. Twenty-nine cases showed numerical abnormalities that involved all chromosomes with the exception of chromosomes 13 and Y, which were gained less frequently and lost more frequently than other chromosomes. Structural abnormalities were found in 30 cases, involving all chromosomes except Y. Chromosomal regions 12p11-13, 13p11-13, 3q26-28, 6q15-16, and 7q31-35 were rearranged in more than 20% of the analyzable cases. No correlation was found between cytogenetic findings and initial characteristics. When compared with diffuse B-cell lymphomas, defects in regions 2p25 (P less than .01), 12p11-13 (P less than .01), 13p11-13 (P less than .01), 14p11 (P less than .01), 15p11-13 (P less than .02), and 20q12-13 (P less than .05) were more frequent in HD. When compared with T-cell lymphomas, only defects in regions 12p12-13 (P less than .01) and 13p11-13 (P less than .01) were more frequent in HD. Failure to obtain analyzable metaphases was correlated with stage IV of the disease (P less than .05) and with a poor survival (P less than .01), but cytogenetic results showed no other correlation with clinical outcome. We conclude that molecular studies in HD should be focused on the short arms of chromosomes 12 and 13. Determination of the clinical significance of cytogenetic findings will require a larger number of patients and a longer follow-up period.