Expression of the p53 protein has been detected recently by immunohistochemistry in Hodgkin's disease (HD), but the relationship between p53 expression and the prognosis and clinicopathological heterogeneity of HD is still unclear. To address these questions we investigated 49 cases of HD for p53 expression by immunohistochemistry using the DO1 monoclonal antibody (MAb) on paraffin sections. Thirty-five cases were simultaneously tested with the 1801 MAb on frozen sections. Thirty-seven of 49 cases (75%) were DO1 positive while 14 of 35 (40%) were PAb 1801 positive. Both MAbs gave a nuclear staining restricted to Reed Sternberg cells (RSCs) and variants and distributed among the three HD subtypes analyzed (ie, nodular lymphocyte predominant, nodular sclerosing, and mixed cellularity). The percentage of positive neoplastic cells in each case was heterogeneous, ranging from almost 100% to less than 5%. In 39 patients for whom clinical data were available statistical analysis did not show any significant correlation between p53-positive immunostaining and clinical staging, B symptoms, probability of relapse, or disease-free survival. We conclude that p53 expression is a common event in HD regardless of histological subtyping, but does not bear any pejorative significance.