Twenty-three patients with marked leukemic involvement by mantle cell lymphoma (MCL) are described. Each patient had an absolute lymphocyte count more than 10 x 10(9)/L. The diagnosis of MCL was supported by compatible immunophenotypic findings and the t(11;14)(q13;q32) in all cases. Morphologically, these cases exhibited a spectrum of findings that we divided into two groups using a cutoff of 20% large or blastoid cells (log rank test, P =.004). Patients with small-cell (<20%) morphologic features survived longer than patients with large/blastoid (> or =20%) morphologic features, (P =.003, log rank test). The most common additional karyotypic abnormality identified in this study involved chromosome 17, in 13 of 23 (56.5%) cases, which correlated with p53 overexpression but not with cytologic features. We conclude that cytologic features of MCL predict the prognosis of patients with marked leukemic involvement. Chromosome 17 abnormalities are common in leukemic MCL, may be involved in pathogenesis, and are associated with p53 expression.