We studied the antigen expression profiles of 19 anaplastic large cell lymphoma (ALCL) cases by multiparameter flow cytometry. The neoplastic cells expressed CD45, HLA-DR, and CD30 in all cases. At least 1 T cell-associated antigen was expressed in each case (CD2, 12/17 [71%]; CD4, 12/19 [63%]; CD3, 6/19 [32%]; CD7, 6/19 [32%]; CD5, 5/19 [26%]; CD8, 4/19 [21%]). CD25 was expressed in 14 (88%) of 16 cases. CD13 was expressed unexpectedly in 8 (47%) of 17 cases. One CD13+ ALCL also was positive for CD33 and 2 others for CD15, CD19, CD20, CD22, CD14, and CD36 were not expressed. Anaplastic lymphoma kinase protein was detected in about 33% (3/9) of ALCLs examined by flow cytometric immunophenotyping (FCI); expression was validated by immunohistochemical analysis. Of 19 ALCL cases, 12 were diagnosed solely based on FCI findings in conjunction with morphologic evaluation of body fluid (1 case), fine-needle aspirate (3 cases), or excisional biopsy specimen (8 cases). The diagnoses of the remaining 7 cases were suggested strongly by FCI and confirmed by immunohistochemical analysis. FCI is useful to aid in diagnosis of ALCL, particularly along with fine-needle aspiration evaluation. ALCL with aberrant expression of myeloid antigens should not be mistaken for extramedullary myeloid tumor.