BACKGROUND:ThinPrep liquid‐based cytology (TP) preparations are being used increasingly in nongynecologic specimens. To the authors' knowledge, few studies to date have evaluated TP cytology in the setting of small cell carcinoma of the lung (SCCL). Accurately differentiating SCCL from other lung tumors has important clinical and therapeutic implications. Herein, the authors evaluated the diagnostic utility and cytomorphology of TP in the setting of SCCL.METHODS:All cases of SCCL with prior or concurrent TP cytologic specimens were identified via computer search. The cytodiagnoses were tabulated. When available, cytologic material was reviewed. Performance parameters of the various cytologic modalities processed with TP were calculated.RESULTS:In 121 patients with SCCL, 261 TP specimens were identified. The cytodiagnoses were: SCCL (119 specimens), suspicious for SCCL (45 specimens), atypical cells‐not otherwise specified (22 specimens), negative/nondiagnostic (63 specimens), and nonsmall cell carcinoma (4 specimens). During the same period of time, 3 cases of false‐positive diagnoses of SCCL were identified. The positive predictive value for a cytodiagnosis of SCCL on TP was 97.5%, and the sensitivity was 62.8%. Bronchial brush was the most sensitive cytologic modality (78.3%). Immunostaining was found to be contributory to the diagnosis in 10 of the 11 cases in which it was attempted.CONCLUSIONS:TP is a sound alternative to conventional preparations for the cytodiagnosis of SCCL. Cytomorphology of SCCL is altered in TP with less molding, less cell fragility, more discohesion, and tumor cell shrinkage artifact. Immunohistochemical staining of cellblocks is a useful adjunct in challenging cases. A positive cytodiagnosis of SCCL on TP can be used to initiate definitive therapy when biopsy is not possible. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.