We read with great interest the case report by Cadavid et al1 in a recent issue of CHEST (January 2011). Although Cadavid et al1 reported an excellent case of extranodal marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT), we would like to raise some concerns about the diagnosis of extranodal MZBL of MALT. To our knowledge, the optimal diagnosis of the disease requires careful integration of morphologic, immunohistochemical, and molecular information, given the nonspecific nature of clinical manifestation, physical examination, and radiographic features.2 It is worth noting that this case report presented only one endobronchial biopsy specimen demonstrating extensive infiltration of the mucosa and submucosa by a homogeneous population of lymphocytes. We question whether it is sufficient to diagnose the disease by histologic examination only. The histologic differentiation between extranodal MZBL of MALT and reactive lymphocytic proliferation may sometimes be difficult.3 This is the reason why some of the patients with extranodal MZBL of MALT are given a misdiagnosis of pneumonia, pulmonary tuberculosis, or interstitial lung disease. Furthermore, extranodal MZBL of MALT typically expresses B-cell-associated antigens, such as CD20 and CD79α, but lacks CD5, CD10, CD23, and cyclinD1. Thus, immunophenotyping is used to exclude B-chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, and follicular lymphomas to aid in the correct diagnosis. We would propose that the authors of this case report supplement immunohistochemistry and/or examine gene rearrangement to validate the diagnosis of extranodal MZBL of MALT.