The p53 gene is a nuclear phosphoprotein that can function as a tumor suppressor gene (Michalovitz et al. 1991). Frequent mutations of the p53 gene have been detected in several types of solid tumors including breast (Mackay et al. 1988), colon (Vogelstein et al. 1989), lung (Yokota et al. 1987), liver carcinoma (Hsu et al. 1991), astrocytoma (Fults et al. 1992), and gliomas (Frankel et al. 1992). In the majority of these tumors with p53 mutations, allelic loss of one copy of human chromosome 17p, the site of the p53 gene has been demonstrated. Such allelic deletion has often been shown to be associated with point mutation on the remaining allele of the p53 gene (for review see Levine et al. 1991). For hematologic malignancies, several reports have demonstrated structural alterations and point mutations of the p53 gene in blast crisis of chronic myelogenous leukemia (CML) (Feinstein et al. 1991) and in acute myeloid leukemia (AML) (Fenaux et al. 1991). In the case of T- and B-cell lymphoid malignancies, a high incidence of p53 mutation was found to be associated with Burkitt lymphoma, B-cell chronic lymphocytic leukemia (B-CLL) but not in other B-cell (Gaidano et al. 1991) or T-cell malignancies (Jonveaux et al. 1991). We have studied the role of the p53 gene in murine lymphoid tumors (Brathwaite et al. 1992) as well as some human astrocytomas (Frankel et al. 1992 and Lang et al. 1992). We describe in this report the analysis of p53 mutations in 92 patients diagnosed with B-cell CLL. We also compared the frequency of point mutations with that of the loss of heterozygosity for chromosome 17p in the same group of patients.