The deletion or mutation of the p53 tumour suppressor gene on chromosome 17p13 is known to be associated with aggressive disease in several B-cell malignancies. The present study describes the p53 gene status in 20 cases of hairy cell leukemia (HCL) and in 12 cases of its morphological variant (HCL-V) by fluorescence in situ hybridization (FISH). A high incidence of p53 deletion was found in both diseases (75-100% of cases). However, a significant difference was observed between the proportion of cells with p53 deletion in HCL-V cases (mean 31%) and HCL cases (mean 12%) P value < 0.01. The observed difference correlates with the well known tendency for transformation and poor response to therapy in HCL-V and seven cases of HCL-V with greater than 22% of cells with p53 deletion showed features of disease progression and transformation. Trisomy 12 was present in 8.5% of the cells in one case of HCL-V and in 6-8% of cells in three cases of HCL.