Pathologic diagnosis of pulmonary involvement with lymphoma has traditionally necessitated open-lung biopsy in most cases. Specimens large enough to allow recognition of characteristic cytologic and architectural changes are usually not obtained bronchoscopically. Even when adequate biopsy specimens are available, however, unequivocal differentiation of lymphoma from benign inflammatory proliferative lesions (for example, pseudolymphoma or lymphocytic interstitial pneumonitis) is not possible on the basis of light microscopic findings alone. Pathologists have relied on immunohistologic examinations in which antibodies directed against B-cell and T-cell surface antigens are used to help distinguish benign from malignant lymphoid proliferations. Unfortunately, even immunohistologic findings may be nondiagnostic, particularly in T-cell lymphomas and in cases in which lymphoma is surrounded by a benign reactive lymphocytosis. Recent development of molecular biologic techniques (for example, Southern blotting) has provided the ability to detect a monoclonal population of cells based on detection of rearrangements of the genes that encode either B-cell immunoglobulin proteins or T-cell antigen receptor proteins. This technique is capable of detecting a clone of cells even when they constitute as little as 5% of a lymphoid infiltrate. Bronchoalveolar lavage can provide samples of sufficient size to facilitate Southern blotting. We present the first case wherein pulmonary involvement with a B-cell lymphoma was confirmed by both immunohistologic and molecular biologic studies of bronchoalveolar lavage fluid.