Combined small cell lung carcinomas (CSCLCs) are small cell lung carcinomas (SCLCs) containing discrete areas of non-small cell morphologic components, found in up to 30% of SCLCs. We assessed immunophenotypic and genotypic similarity between the distinct morphologic constituents in 7 CSCLCs. Each was stained for synaptophysin, CD56, chromogranin, bcl-2, thyroid transcription factor (TTF)-1, cytokeratin 7, and PAX-5. Loss of heterozygosity (LOH) analysis was performed using markers on 3p (2 loci), 17p (3 loci), 17q (1 locus), and 22q (2 loci). The distinct components shared an identical immunophenotype in 6 cases; all were positive for synaptophysin and CD56 in both components. LOH analysis revealed shared loss of least 1 marker in every lesion, including LOH at 22q13 (characteristic of SCLC) in 5 tumors. The individual elements constituting CSCLCs are closely related in most cases despite their distinct morphologic appearances. The prevalent expression of synaptophysin and CD56 and loss of 22q13 suggest that these tumors are biologically closer to SCLC.