The cases are presented of three patients with large cell malignant lymphoma of the mediastinum with a distinctive growth pattern characterized by marked tropism of tumor cells for germinal centers. The patients' ages ranged from 35 to 70 years; one was a woman, and two were men. Histologically, the lesions were characterized by a proliferation of large atypical cells arranged in clusters that encroached on mantle zones and invaded germinal centers. Immunohistochemical studies showed positive staining of the tumor cells for leukocyte common antigen, L-26 (pan-B-cell antigen), and lambda light chain restriction and negative staining with Leu-M1, UCHL-1 (pan-T-cell antigen), Ber-H2 (Ki-1 antigen), S-100 protein, HMB-45, low-molecular weight keratins, epithelial membrane antigen, carcinoembryonic antigen, and placental alkaline phosphatase. Electron microscopy done on one specimen showed cells with abundant cytoplasm, some of them containing surface microvilli, scant organelles, and scattered polyribosomes consistent with lymphoid cells. Because of their unusual growth pattern and morphology, these tumors can be mistaken for primary or metastatic carcinomas, germ cell tumors (particularly seminomas), and metastatic malignant melanomas. It is proposed that the "germinotropic" features observed in these lesions are the result of active colonization of germinal centers by the tumor cells. The possible pathogenetic implications of this phenomenon are discussed.