CD30/Ki-1 antigen expression in 243 cases of malignant lymphomas was examined using Ber-H2 monoclonal antibody. Among them 20 cases were categorized as Ki-1 anaplastic large cell lymphoma. In two of these cases histiocyte-associated markers were also expressed. In these cases histopathologic and extensive in situ immunophenotypic analyses were used with genotypic studies in the determination of cell lineage. A sinusoid histologic pattern of involvement with partial lymph node infiltration by pleomorphic neoplastic cells was noticed in the nodes from both patients. Solid areas of node replacement resembling metastatic carcinoma were seen in Patient 1. Immunohistologically, tumor cells of both cases were positive for CD30, CD25, CD71, LN3 (HLA-DR), EMA, CD45, CD74, vimentin, alpha-1-antichymotrypsin, and CD68. Patient 1 was also CD45RO+, CD43+, whereas Patient 2 was positive for alpha-1-antitrypsin and CD4 tumor cells. Genotypic studies revealed that TCR beta and TCR gamma chain genes were clonally rearranged in Patient 1, whereas no rearrangements were detected in Patient 2. This study supports the view that some Ki-1 anaplastic large cell lymphomas may express multiple histiocyte-associated antigens and confirms that this group of neoplasms have immunophenotypic heterogeneity. The results of genotypic analyses used with immunophenotyping does not exclude that the tumor cells in these cases may be of true histiocytic origin despite the Ki-1-positive phenotype.