Histiocytic sarcoma (HS) and histiocyte-associated lymphoma (HAL) of mice are difficult to distinguish histologically. Studies of multiple cases initially diagnosed as HS or HAL allowed us to define HS as round, fusiform, or mixed cell types that were F4/80+, Mac-2+, and PAX5-; that lacked markers for other sarcomas; and that had immune receptor genes in germline configuration. Two other subsets had clonal populations of lymphocytes. The first, HAL, featured malignant lymphocytes admixed with large populations of normal-appearing histiocytes. The second appeared to be composites of lymphoma and HS. Several cases suggestive of B myeloid-lineage plasticity were also observed.