Expression of KP1 /CD68 macrophage-associated antigen in a series of 840 selected malignant neoplasms, including immunomorphologically characterized cases of non-Hodgkin’s lymphoma (NHL) (434), I lodgkin’s disease (HD) (115), soft tissue sarcoma (147), carcinoma (49), and other tumors (95), was examined. KP1 expression was detected in a significant number of NHLs (107 of 434; 24.7%), most of them (65 of 107; 60.7%) of the diffuse small cell subtype. Only 14 of the 155 large cell lymphomas, compared to 10 of the 51 Ki-1/CD30+ anaplastic large cell (ALC) lymphomas examined, were KP1 positive. Conversely, none of the T-lineage NHL—other than Ki-1/CD30+ ALC lymphomas—or the HD cases tested was labeled by KP1 antibody. Among the other neoplasms tested, KP1 was reactive with a variable proportion of cases of malignant fibrous histiocytoma (19 of 24; 79.2%), malignant schwannoma (8 of 22; 36.4%), liposarcoma (3 of 9; 33.3%), leiomyosarcoma (8 of 37; 21.6%), cutaneous or metastatic melanoma (51 of 73; 69.9%), and renal cell carcinoma (3 of 5; 60%). These results indicate that KP1 shows a relatively wide spectrum of immunoreactivity with malignant neoplasms of presumed non-histiocyte origin, thus arguing against its expected specificity and high value in diagnostic pathology. Although the significance of KP1 expression by some subsets of NHLs remains to be elucidated, its close association with B-cell NHLs, mostly of the diffuse small cell type, should stimulate further pathologic and clinical investigations.