Context.-A vast majority of neoplasms arising from lung or pleura are initially diagnosed based on the histologic evaluation of small transbronchial, endobronchial, or needle core biopsies. Although most diagnoses can be determined by morphology alone, immunohistochemistry can be a valuable diagnostic tool in the workup of problematic cases. Objective.-To provide a practical approach in the interpretation and immunohistochemical selection of lung/pleura-based neoplasms obtained from small biopsy samples. Data Sources.-A literature review of previously published articles and the personal experience of the authors were used in this review article. Conclusion.-Immunohistochemistry is a useful diagnostic tool in the workup of small biopsies from the lung and pleura sampled by small biopsy techniques.