A B-cell anaplastic large cell lymphoma, confirmed by immunohistochemistry and Southern blot immunoglobulin gene rearrangement analysis, contained neoplastic cells that were immunoreactive for cytokeratin using antibodies CAM 5.2, M20, MAK 6, and KS-B17.2. Bands corresponding to cytokeratin 18 and cytokeratins 18 and 8 were seen on Western blot immunoanalysis using antibodies KS-B17.2 and CAM 5.2. The lymph node also contained cytokeratin-positive extrafollicular fibroblastic reticulum cells. Although it is possible that the presence of cytokeratin in the cells of anaplastic large cell lymphoma represented phagocytosed filaments from the reticulum cells, it is more likely that the cytokeratins were synthesized by the malignant cells. The finding of cytokeratin in anaplastic large cell lymphoma, although infrequent, adds to the confusion in the diagnosis of this pleomorphic neoplasm.